Transcript Principles of antimicrobial treatment

Antibiotics in Urology
Claire Kingston
Pharmacist SVUH
Jan 31st 2014
Introduction – Urinary tract Infection
(UTI)
• 2nd most common clinical indication for empirical
antimicrobial treatment
• Inappropriate and unnecessary use of antibiotics
associated with problems such as Clostridium
difficile infection (CDI), MRSA, VRE
• Evidence-based antibiotic guidelines are key to
improving prescribing, reducing resistance &
optimising patient outcomes
• Antimicrobial Prescribing in Primary Care (2011)
now available on
http://www.antibioticprescibing.ie/
Principles of antimicrobial treatment
– empirical prescribing
• Treat patient not result
• Ensure provisional clinical diagnosis
documented & specimens taken before start of
therapy.
• Broad spectrum empirical therapy for severe
infections, then de-escalate once causative
organism identified.
• Check C/I, allergies, interactions, adverse
effects.
• IV route initially if severe infection, or unable to
tolerate oral drugs. Review Rx after 48 hours .
Principles of antimicrobial treatment
• Local policies often limit drugs use based on
economics & local resistance
• Sample should be taken for C+S testing before
starting therapy - will identify the causative
pathogen & its susceptibility pattern.
• Dose may vary depending on age, weight,
hepatic & renal function, severity of infection
• Route may depend on severity on infection
• Duration depends on infection & response
DAY 1
START SMART…
THEN…
a) Do not start
antibiotics if no
clinical evidence of
DAY 2 …. ONWARDS
bacterial infection
b) Obtain cultures first
c) EMPIRIC
TREATMENT
BASED ON
ANTIMICROBIAL
GUIDELINES or
BASED ON
MICROBIOLOGY
ADVICE
REVIEW
TREATMENT
FOCUS
1. STOP ANTIBIOTICS
2. CONTINUE
ANTIBIOTICS/ PLAN
TREATMENT/
COURSE
3. CHANGE
ANTIBIOTICS/
PLAN/TREATMENT
COURSE
4. SWITCH TO PO IF
APPROPRIATE
5. CONSIDER OPAT IF
APPROPRIATE
ALWAYS DOCUMENT INDICATION
FOR THE ANTIMICROBIAL AND
TREATMENT PLAN IN THE MEDICAL NOTES
Adapated from ARHAI Antimicrobial Stewardship Guidance Nov 2011
Classification of antibiotics:β-lactams
• Penicillins
–
–
–
–
Benzylpenicillin, phenoxymethylphenicillin
Penicillinase-resistant, e.g. flucloxacillin
Broad-spectrum, e.g. amoxycillin, co-amoxiclav
Antipseudomonal, e.g.Tazocin, Timentin 
• Cephalosporins e.g. cephalexin, ceftriaxone
• Carbapenems – e.g. ertapenem, meropenem
– Meropenem used for complicated UTIs & severe
hospital infxns.
– Ertapenem – seizure potential. Resistance
• Other beta-lactams – e.g. aztreonam
Penicillins – Hypersenstivity
• Allergies in 1-10% patients, anaphylaxis in
0.05%
• Greater risk if history of atopic allergy
• If history of anaphylaxis, urticaria or rash
immediately after penicillin – do not give
penicillins or cephalosporins
• If history of minor rash (non-pruritic, small area)
more than 72 hours after drug – may not be
allergic
• 0.5-0.65% penicillin-sensitive patients will also
be allergic to cephalosporins
• Aztreonam less likely to cause hypersensitivity.
Classification of antibiotics
(contd)
•
•
•
•
Aminoglycosides – e.g.gentamicin
Glycopepdidases – e.g. teicoplanin, vancomycin
Macrolides – e.g. clarithromycin
Quinolones – e.g. ciprofloxacin
- Ensure adequate fluid intake (risk of crystalliuria)
- May impair performance of skilled tasks
- Caution if history of seizures
- Photosensitivity reactions
- Prolongs QT interval
- Give > 1 hour before ( or > 4 hours after) Mg, iron, dairy
products
Aminoglycoside once-daily dosing
e.g. gentamicin
• Total dose should be specified on Rx. Use accurate
weight.
• If patient is obese use dosing weight calculator to
calculate dose (www.UptoDate.com)
• Usual dose 5mg/kg/day (normal renal function) or
2mg/kg/day if serum creatinine >120 umol/L or GFR
<80ml/min
• Take level before 2nd or 3rd dose and 18-24 hours after
last dose (= trough).
• Give (ideally) at 6pm to facilitate morning assay
• Check levels 2-3 times weekly in patients < 50 years and
every 2nd day if > 50 years. If renal function abnormal, do
daily levels.
• Target level < 1mg/l
Classification of antibiotics
(contd)
• Trimethoprim
- synergistic with sulfamethoxazole (cotrimoxazole)
- serum creatinine may rise due to competition for renal excretion
- may cause hyperkalaemia in severe renal impairment
- Stevens Johnson’s syndrome & blood dyscrasias rare
• Tetracyclines – e.g. doxycycline, (Tigecycline)
• Nitrofurantoin
- can cause peripheral neuropathy
- avoid in GFR < 20mls/min as inadequate urine conc & toxicity
(blood dyscrasias, neuropathy)
- pulmonary reactions (e.g.pulmonary fibrosis) reported
• Others – e.g. daptomycin, linezolid, sodium fusidate,
colistin, metronidazole, clindamycin, rifaximin
Extended Spectrum B-lactamases
(ESBLs)
• Enzymes produced by some bacteria that
provide resistance to extended spectrum (3rd
generation) cephalosporins, & monobactams
(aztreonam). Don’t affect carbapenems.
• Beta-lactamase provides antibiotic resistance by
breaking the antibiotic’s structure.
• Gram-negative enteric bacteria, in particular K
pneumoniae and E coli, are involved
• ESBLs are multi-resistant but remain sensitive to
nitrofurantoin
Classification of urinary & male
genital tract infections
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Uncomplicated lower UTI (cystitis)
Uncomplicated pyelonephritis
Complicated UTI +/- pyelonephritis
Urosepsis
Urethritis
Prostatits, epididymitis, orchitis
Significant bacteriuria in adults
• 1. ≥ 103 uropathogens/mL of midstream urine in acute
uncomplicated cystitis in female.
• 2. ≥ 104 uropathogens/mL of midstream urine in acute
uncomplicated pyelonephritis in female.
• 3. ≥ 105 uropathogens/mL in midstream urine of women or
104 uropathogens/mL of midstream urine in men (or in
straight catheter urine in women) with complicated UTI.
• 4. In a suprapubic bladder puncture specimen, any count of bacteria
is relevant.
• 5. Asymptomatic bacteriuria = two positive urine cultures taken ≥ 24
hours apart containing ≥ 105 uropathogens/ml of the same bacterial
strain.
Acute, uncomplicated UTIs
• Includes acute cystitis & acute pyelonephritis
• Mostly in women without structural & functional
abnormalities within the urinary tract, kidney
diseases or co-morbidity
• E.coli responsible for 70-95% cases, S.
saprophyticus in 5-10% cases
Treatment for Acute Uncomplicated
Cystitis
1.
2.
3.
4.
5.
Nitrofurantoin 50-100mg QDS for 3 - 7 days – low resistance &
S/E, high efficacy. Activity effected by urinary pH - avoid
alkalinising agents if on.
Trimethoprim 200mg BD for 3 days or Trimethoprimsulfamethoxazole 160/800mg BD for 3 days (if resistance rate <
20%).
-lactams (e.g. co-amoxiclav, cephalexin), – inferior efficacy &
increased adverse effects. Only use if others can’t be used – used
based on local resistance rates. Amoxicillin/ampicillin should not
be used (resistance/poor efficacy).
Fluoroquinolones (e.g. ciprofloxacin) – efficacious but high S/E –
not recommended routinely. Reserve for resistant infections with
limited option & confirmed by C + S results.
Fosfomycin 3g stat – minimal resistance & S/E but may be less
efficacious –microbiology advice.
Prophylaxis with probiotics /
cranberry
• Probiotics:
– Oral probiotics – may restore vaginal lactobacilli,
compete with urogenital pathogens & prevent
vaginosis
– Intravaginal probiotics once/twice weekly – L.
rhamnosus GR-1 & L. reuteri RC-14
• Cranberry:
– Some evidence (min 36mg proanthocyanidin A) may
reduce rate of lower UTIs is women, but small
number of weak clinical studies. Can increase INR.
UTIs in men
• Acute, uncomplicated UTIs in young men: need
at least 7 days treatment
• Most men with febrile UTI have concomitant
prostate infection ( PSA & prostate volume). If so
 2 weeks treatment ( up to 3 weeks) is
recommended preferably with a fluoroquinolone.
Complicated UTIs due to urological
disorders
• Infection associated with a condition such as a structural
or functional abnormality of genitourinary tract, or
underlying disease that interferes with host defences
• Broad range of bacteria responsible – larger spectrum & 
resistance than uncomplicated UTIs
• Enterobacteriacae predominate, E. coli most common
pathogen. Pseudomonas, serratia & + cocci (e.g.
staphylococci & enterococci) also involved
• Proteus & pseudomonas particularly common with
urinary stones
• Need 7-14 days treatment
Treatment for Acute Pyelonephritis
•
•
•
If no healthcare contact or antibiotic therapy in
past 6 months:
Ciprofloxacin 500mg BD for 7 days (+/- 400mg
IV stat) for mild-moderate infection if
resistance < 10%. Can be +/- gentamicin.
Trimethoprim 200mg BD for 14 days or
Trimethoprim-sulfamethoxazole 160/800mg
BD if sensitivities allow.
Oral -lactams less effective. Co-amoxiclav
500/125mg TDS for 14 days may be option.
Treatment for Acute Pyelonephritis
If healthcare contact or antibiotic therapy in past
6 months:
• Piperacillin-tazobactam 4.5g 8 hourly IV
(Aztreonam 2g 8 hourly IV if penicillin rash or
anaphylaxis) PLUS
• Gentamicin once daily IV
• Usually 14 day treatment
Catheter associated UTIs (CAUTIs)
• Most are derived from the patient’s own colonic flora
• Duration of catheterisation is most important risk factor
(> 30 days)
• While catheter in place, treatment of asymptomatic
catheter-asociated bacteriuria is not recommended.
• Routine urine cultures in asymptomatic catheterised
patients not recommended
• Urine (& in septic patients, also blood cultures) should be
taken before antimicrobial therapy is started to guide
therapy
• 7 days course of antibiotic reasonable.
Change or removal of urinary
catheter
• Ciprofloxacin 500mg PO 1 hour prior to
removal
OR ciprofloxacin 400mg IV immediately
prior to removal
OR gentamicin 2mg/kg IV immediately
prior to removal
Transrectal prostate biopsy
• Ciprofloxacin 750mg PO AND amikacin
500mg IM one hour pre-procedure.
• Give second dose of Ciprofloxacin 750mg
12 hours post-procedure
• Check recent urine culture results and
modify as necessary
References
• BNF, 66th edition (2013)
• European Society of Urology Guidelines
(2013)
• SIGN 88 – Management of suspected
bacterial urinary tract infection in adults
(2012)
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