Transcript ID BOARD REVIEW 2009 Amanda Peppercorn, M.D. Assistant Professor of Medicine

ID BOARD REVIEW 2009
Amanda Peppercorn, M.D.
Assistant Professor of Medicine
University of North Carolina at Chapel Hill
Toxic Shock Syndrome
 Group A Strep:



Any invasive GAS infection (bacteremia, nec fasc, gangrenous myositis
“flesh eating”) complicated by case definition of TSS
Exotoxin superantigens (complicated about 1/3 of invasive GAS infections)
Associated bacteremia common
 Staph aureus toxins:






Food poisoningstaph enterotoxin
Staph Scalded Skinexfoliative toxin
CA-MRSAPanton-valentine leukocidin toxin
TSSTSST-1 superantigen (interact directly with invariant region of MHC II
molecule with activation of up to 20% of all T cells with massive cytokine
storm)
Previous association with tampons
Usually MSSA but MRSA has been reported
Desquamation
TSS Case Definition
 Fever: T>38.9C (102.0F)
 Hypotension:
 SBP<90 or <5 percentile by age for children<16 years of age
 orthostatic drop in DPB>15mmHg
 orthostatic syncope/dizziness
 Rash: diffuse macular erthyroderma
 Desquamation: 1-2 weeks after onset of illness, usually palms and
soles
 Multisystem involvement (3 or more)






GI (vomiting, diarrhea at onset of illness)
Muscular (severe myalgias, elevated CPK)
Mucous Membranes (vaginal, oropharyngeal or conjunctival hyperemia)
Renal (creatinine>2 times ULN or pyuria>5 WBC)
Hepatic (elevated bilirubin or transaminases>2 times ULN
Hematologic (platelets<100K)
Treatment
 Supportive, often hemodialysis, pressors, ICU care (intractable
hypotension/capillary leak)
 Strep:




Emergent surgical debridement if soft tissue primary source (“pain out of
proportion to exam”)
Empiric: Clinda (900 iv q8) + imi/dori/meropenem or pip/tazo Taylored:
PCN G + Clinda
IVIG
?immunomodulators ex TNFa inhibitors?
 MSSA: clinda + oxacillin/naf/cefazolin, IVIG
 MRSA: clinda + vancomycin, IVIG
NECROTIZING INFECTIONS
 Necrotizing fasciitis, type 1
 Mixed infection; anaerobes plus strep or GNR
 Incubation = 48-96 h; progression = hrs – days
 Marked pain, tenderness, swelling, crepitus, foul-smelling
 Necrotizing fasciitis, type 2
 Grp A strep (“flesh-eating” bacteria)
 Incubation = 6-48 h; progression = a few days
 Often with toxic shock, bullae, no crepitus
 Pain out of proportion to exam
Acute Sinusitis











Acute: Fever, facial pain, edema, erythema, maxillary toothache
Subacute: Presumed viral sinusitis with no improvement in 7d
S. pneumoniae H. influenzae M. catarralis
Also MRSA, aspergillus, anaerobes from mouth flora (rare)
Amoxicillin/Clavulanate 875 mg PO Q12h x 10 d
Levofloxacin 750 mg PO Q24h x 10 d
Reserve antibiotics for patients failing decongestant therapy
and facial pain, purulent discharge and/or severe illness
Treatment for full duration of therapy is essential to prevent
relapses
Supportive therapy: decongestants and antihistamines
Complications: extension through bone to brainbrain abscess
Diabetics, immunocompromised: think rhinocerebral Mucor
Actinomycosis
 Branching filamentous anaerobic gram positive rod, “higher order






bacteria” ;appearance like a fungus
Characteristic sulfur granules (balls of organisms) in
tissue/pathology samples
Normal part of oral flora
Cause oropharyngeal disease (dental abscess, jaw osteo, etc)
Also cause of uterine infection (IUDs), abdominal abscesses
Differentiate from nocardia by anaerobic principally and modified
AFB stain (nocardia+, actino negative)
Treatment: PCN, cephalosprins (keflex), clinda
Physiology and Resistance Mechanisms of S aureus
 S aureus is a virulent human pathogen
with the ability to elaborate a range of
virulence factors and toxins; gram
positive cocci in clusters
 Resistance to methicillin first
appeared in 1961, attributed to
inheritance of a mecA gene found on
the mobile staphylococcal cassette
chromosome mec (SCCmec)
 Genetic analysis suggests that mecA
has been transferred to S aureus over
20 times, resulting in 5 major lineages
 MecA gene cassette leads to genetic
alteration of penicillin binding protein,
WTA=wall teichoic acid; PVL=Panton-Valentine leukocidin;
conferring resistance to all penicillin
CHIP=chemotaxis inhibitory protein.
and cephalosporin family of
Zetola N et al. Lancet Infect Dis. 2005;5:275-286.
antibiotics
Deresinski S. Clin Infect Dis. 2005;40:562-573.
Foster TJ. J Clin Invest. 2004;114:1693-1696.
COMPARISON:
CA-MRSA AND HA-MRSA
CA-MRSA
HA-MRSA
Clinical spectrum
Skin and soft tissue
Respiratory tract, UTI,
bloodstream infections
Epidemiology
Clusters and outbreaks in
closed populations
Healthcare-associated
outbreaks
Underlying condition Dermatological
HAI risk factors
Age group
Younger
Older
Resistance pattern
Susceptible to multiple
antibiotics
Resistant to multiple
antibiotics
Genotype
sccMec IV
PVL present
sccMec I, II, or III
Race/ethnicity
Virulence
PVL absent
Diederen BMW, et al. JID 2006;52:157-168
Risk Factors for CA-MRSA
 Athletes (close phyical contact)
 Military personnel
 Children
 Native Americans
 HIV
 MSM
 Prisoners
 Young sexually active
 Family members (don’t forget to ask!)
 Majority of patients have no identifiable risk factors
Syphilis
 Early: primary--painless chancre, secondary (weeks to couple





months after primary)—rash (infectious) rarely pustular, condyloma
lata (MM, moist areas) and systemic sx (fever, HA, malaise, LAD),
early latent (first year)
Late: late latent, tertiary (gummas, cardiovascular, neurosyphilis—
uveitis, ocular nerve damage, dementia, paresis, tabes dorsalis,
meningitis, cranial neuropathies)
HIV: primary and secondary can overlap
Syphilis: a reportable disease
Treatment: early—IM PCN, doxy as alternative, neurosyphilis—IV
PCN x 14 days
Response to treatment: 4 fold decrease in VDRL/RPR at 1 year
Palmar involvement—secondary syphilis
Labial Condyloma Lata, Secondary
Syphilis
CDC ISOLATION GUIDELINES
Isolation Precautions
 Standard precautions
 Airborne precautions
 Special airborne precautions
 Droplet precautions
 Contact precautions
 Protective precautions
STANDARD PRECAUTIONS
 Hand hygiene: Before and after each patient contact &
after gloves removed

The wearing of artificial fingernails or extenders is prohibited
(based on CDC guidelines)
 Gloves: When touching contaminated items (blood,
body fluids, secretions, excretions)
 Mask, eye protection, face shield: Whenever splashes
or sprays of body fluids possible
 Gown: Whenever splashes or sprays of body fluids
possible
AIRBORNE PRECAUTIONS
Isolation
 Private negative pressure room
 Direct out exhausted air
 N95 respirator
Representative pathogens
 M. tuberculosis
 Varicella, Zoster
(immunocompromised)
 Measles
SPECIAL AIRBORNE PRECAUTIONS
Isolation
 Airborne + eye shields
Representative pathogens
 Avian influenza
 Monkeypox
 SARS Co-V
 Smallpox
 Viral hemorrhagic fever (e.g.,
Ebola, Lassa)
DROPLET PRECAUTIONS
Isolation
 Private room
 Mask
Representative pathogens
Invasive N. meningitidis
RSV
Bordetella pertussis
Rubella, Mumps
Group A streptococcal
pharyngitis
 Invasive H. influenzae





CONTACT PRECAUTIONS
Isolation
 Gloves
 Gowns
Representative pathogens
 Clostridium difficile
 HSV
 Varicella/zoster
 VRE, MRSA
 MDR pathogens (resistant to
two or more classes of
pathogens)
BOARD REVIEW QUESTIONS:
INFECTION CONTROL
 #42 – TB – airborne, removal isolation
 #61 – Varicella = airborne + contact
 #88 – Tularemia = no person-to-person
 #113 – C. difficile = contact + enhanced
environmental cleaning (spores)
POST-EXPOSURE PROPHYLAXIS











Animal bite wound
Anthrax
Avian influenza
Diphtheria
Hepatitis A
Hepatitis B
HIV
Human bite wound
Influenza A
Influenza B
Measles










Meningococcal infection
Monkey bite (B virus)
Monkeypox
Pertussis (whooping cough)
Rabies
Smallpox
Syphilis
Tuberculosis (TB)
Varicella (chickenpox)
Zoster (shingles)
POST-EXPOSURE PROPHYLAXIS
USING VACCINES
 Hepatitis B*: <7 days (alternative HBIG)
 Measles: <3 days (alternative Ig)
 Rabies*: ASAP (plus RIG); prior to symptoms
 Tetanus*: Post-wound (no time limit)
 Small Pox: <4 days
 Varicella: <4 days (alternative VZIG or acyclovir)
 Outbreak control: Hepatitis A, pertussis, meningococcal
* May need to be provided with an immunoglobulin preparation
POST-EXPOSURE PROPHYLAXIS USING ANTI-INFECTIVES
 Animal bite: Amoxacillin-sulbactam x 5 days
 Influenza: Oseltamivir or zanimivir
 Lyme disease: can offer Doxy 200 mg x 1 (with many
caveats—definite Ixodes, long attachment—36hrs, high
endemic region—20% ticks with disease, present within
72hrs, adults and children>8, non-pregnant)
 Meningococcus: Ciprofloxaxin 400 mg (alternative
ceftriaxone IM)
 Pertussis: Azithromycin x 5 days (alternative TMP-SMX
for 7-14 days)
 HIV: combination antiretrovirals, data supports starting
ASAP, no benefit after 72 hours (CDC 36 hours)
NO POST-EXPOSURE PROPHYLAXIS
 Adenovirus conjunctivitis
 Hepatitis C
 Mumps
 Parvovirus B19
 Rubella
 Severe acute respiratory distress syndrome (SARS)
PATHOGENS ASSOCIATED WITH SKIN
AND SOFT TISSUE INFECTIONS
Cat bite
Dog bite
Human bite
Rat bite
Snake bite
Shark bite
Pig bite
Animal hides
Pasteurella sp (P. multocida), Franciscella tularensis
P. multocida, Capnocytophaga canimorsus, CDC group
EF-4
Eikenella corrodens, Fusobacterium, streptococci,
Preotella, etc.
Spirillum minor (systemic = Streptobacillus moniliformis)
Aeromonas hydrophila
Vibrio carchariae
Erysipilothrix rhusiopathiae
Bacillus anthracis, Franciscella tularensis
PATHOGENS ASSOCIATED WITH SKIN
AND SOFT TISSUE INFECTIONS
Injection drug use
Salt water injury
Fresh water injury
Fish tank exposure
Fishmonger
Medicinal leeches
Hot tubs
Plant/soil exposure
Soil contamination
S. aureus, Clostridium sp., E. corrodens, Grp A strep
Vibrio Vulnificus
Aeromonas hydrophila
Mycobacterium marinum
Erysipilothrix rhusiopathiae, Streptococcus iniae
A. hydrophila, Aeromonas sobria, Vibrio fluvialis
Pseudomonas aeruginosa
Sporotrichosis
Nocardia, Clostridium sp., Serratia
TREATMENT OF MRSA: ORAL THERAPY
 Oral regimens (use only after susceptibility testing)
 Linezolid (expensive)
 Clindamycin (use only if erythromycin susceptible or D test
performed to confirm susceptibility)
 Trimethoprim-sulfamethoxazole
 Minocycline
 Monitoring
 Daptomycin: CPK each week; stop if CPK >5x ULN
(symptomatic) or >10x ULN (asymptomatic) or >1000 U/L
 Linezolid: CBC with platelets each week; do not treat >28 days
BOARD REVIEW QUESTIONS:
SKIN
 #68 – Osteo in drug user
 #71 – Human bite
 #83 – Cat bite
 #85 – IDU joint infection
 #94 – SA infection
 #107 - NTM
CAP: PATHOGENS
Outpatient
Inpatient (non-ICU) Inpatient ICU
S. pneumoniae
M. pneumoniae
H. influenzae
C. pneumoniae
Respiratory viruses*
S. pneumoniae
M. pneumoniae
C. pneumoniae
H. Influenzae
Legionella spp.
Aspiration
Respiratory viruses*
S. pneumoniae
S. aureus
Legionella spp.
Gram-negative bacilli
H. influenzae
* Influenza A and B, adenovirus, RSV, parainfluenza
Mandell LA, et al. Clin Infect Dis 2007;44(suppl 2):27-72
CAP THERAPY: OUTPATIENTS
 Previously healthy and no risk factor for DR-SPn
 No recent antibiotics: Macrolide (I), doxycycline (III)
 Recent antibiotics: FQ, advanced macrolide + high-dose
amoxicillin, advanced macrolide + high-dose amoxicillin/clav
 Comorbidities: Chronic heart, lung, liver, or renal
disease


No recent antibiotics: Advanced macrolide, FQ
Recent antibiotics: FQ (I), -lactam + macrolide (I), -lactam
+ doxycycline (II) {-lactam = high dose amoxicillin or amoxclav}
 Regions with >25% high level macrolide resistant SPn
use alternative agent
CAP THERAPY: INPATIENTS,
NON-ICU
 Non-ICU
 FQ (I)
 -lactam + macrolide (I)
 -lactam = cefotaxime, ceftriaxone, ampicillin
 ICU
 -lactam + FQ (I)
-lactam = cefotaxime, ceftriaxone, ampicillin-sulbactam
 -lactam + advanced macrolide (II)
-lactam = cefotaxime, ceftriaxone, ampicillin-sulbactam
Advanced macrolide = azithromycin or clarithromycin
Pneumococcus
 50% resistance at UNC to all macrolides (mechanism: alteration of ribosome





binding site)
Vanc susceptible--universal
Resistance an issue for:
 Beta-lactams (penicillins, cephalosporins, and carbapenems) : 20% PCN
R, 5% Cephalosporin R
 Macrolides (erythromycin, azithromycin, clarithromycin and lincosamines
(clindamycin)
 Tetracyclines and folate inhibitors (trimethoprim-sulfamethoxazole [TMPSMX])
Fluoroquinolones (ciprofloxacin, levofloxacin, gemifloxacin, moxifloxacin)
Meningitis: vanc (to cover R pneumococcus), ctx (better CNS penetration,
good for meningococcus and pneumoncoccus), steroids (particularly for
pneumococcus, to prevent hearing loss and other long term complications)
although steroids may decrease CNS penetration of vancomycin; ampicillin
for young and old and immunocompromised (to cover listeria)
No steroids in places with HIV prevalence and presumed meningitis
BROAD SPECTRUM ANTIBIOTICS
 Carbapenems: Imipenem, meropenem (not ertapenem)
 Coverage: GPC, GNRs, P. aeruginosa, anaerobes
 Holes: MRSA, Listeria, Legionella
 Piperacillin-tazobactamn (not ticar/clav or amp/sulbactam)
 Coverage: GPC, GNRs, P. aeruginosa, anaerobes, enterococci
 Holes: MRSA, Listeria, Legionella
 Tigecycline
 Coverage: GPC (including MRSA, VRE), GNRs (including ESBL
producers and Acinetobacter), anaerobes
 Holes: Pseudomonas aeruginosa, Proteus spp.
BROAD SPECTRUM ANTIBIOTICS:
USES
 Sepsis of unknown etiology (GPC, GNR)
 Neutropenic fever (GNR, PA, SA)
 Severe intra-abdominal infections (GNR, Enterococcus,
anaerobes)
 Gangrenous soft tissue infections (diabetic) (GNR, PA,
SA)
 Known resistant pathogens (ESBL, Acinetobacter,
Burkholderia, Pseudomonas)
Endocarditis
 Updated Duke Criteria: 2-1/3-5 (major/minor criteria)
Major: sustained bacteremia by organism known to cause
endocarditis (SA, S viridans, enterococcus, HACEK, CNS with pv),
endocardial involvement seen by echocardiogram (vegetation,
abscess OR new valvular regurgitation*)
 Minor: predisposing condition (PPM/vascath, HD, IVDA), fever,
vascular signs (septic emboli, janeway lesions, mycotic aneurysms),
immune complex phenomena (osler nodes, roth spots,
glomerulonephritis) +blood culture not meeting standard criteria
 Categories: native valve (bicuspid, calcification, prior endocarditis, any
valvular disease), prosthetic valve (high mortality, need rifampin/gent,
often requires surgery), IDU (can use shorter course of treatment with
right sided)
 Culture negative: q fever, brucella, bartonella, legionella, chlamydia,
HACEK, nutritionally deficient strep
 Indications for valve surgery: persistent bacteremia, refractory CHF,
myocardial abscess/purulent pericarditis, difficult organisms (PsA,
yeast, MRSA), recurrent septic embolic complications, large
vegetation

Tuberculosis
 PPD treatment:
 >5mm: HIV, immunosuppressed (TNF inhibitor, prednisone 15 mg/d x
1 month), known close contact
 >10mm: all other high risk populations (prisoners, healthcare worker,
RF, homeless, immigrants, DM, malignancy, hx gastrectomy,
malnutrition, etoh, long-term care)
 >15mm: everyone else
 Treatment: rule out active disease by CXR and symptom screening
 TB considerations: BCG (no change in interpretation, esp if >5 years
ago), prophylaxis and treatment in setting of MDR
 Primary diseasedisseminationcontrol or active disease (lungs,
LNs, pleurisy, CNS—tuberculomas, basilar meningitis, GI, GU—
uterine, kidneys, bone—Potts disease, neck LN—Scrofula), HIV,
miliary
AHA Guidelines for Endocarditis
Prophylaxis 2007 Update
 IE is much more likely to result from frequent exposure to
random bacteremias associated with daily activities (eg, tooth
brushing) than from bacteremia caused by a dental,
gastrointestinal, or genitourinary procedure.
 Prophylaxis may prevent an exceedingly small number of cases
of IE, if any, in individuals who undergo these procedures.
 The risk of antibiotic-associated adverse events exceeds the
benefit, if any, from prophylactic antibiotic therapy.
 Maintenance of optimal oral health and hygiene may reduce the
incidence of bacteremia from daily activities and is therefore
more important than prophylactic antibiotics for a dental
procedure to reduce the risk of IE.
Updates
 Patients with the following cardiac conditions were considered to
meet this criterion:







Prosthetic heart valves, including bioprosthetic and homograft
valves
Prosthetic material used for cardiac valve repair
A prior history of IE
Unrepaired cyanotic congenital heart disease, including palliative
shunts and conduits.
Completely repaired congenital heart defects with prosthetic material
or device, whether placed by surgery or by catheter intervention,
during the first six months after the procedure.
Repaired congenital heart disease with residual defects at the site or
adjacent to the site of the prosthetic device.
Cardiac "valvulopathy" in a transplanted heart. Valvulopathy is
defined as documentation of substantial leaflet pathology and
regurgitation
 No longer indicated — Common valvular lesions for which antimicrobial
prophylaxis is no longer recommended include bicuspid aortic valve, acquired
aortic or mitral valve disease (including mitral valve prolapse with regurgitation
and those who have undergone prior valve repair), and hypertrophic
cardiomyopathy with latent or resting obstruction
 Procedures that may result in transient bacteremia and are
recommended for prophylaxis —





All dental procedures that involve manipulation of either gingival tissue or the
periapical region of teeth or perforation of the oral mucosa.
Procedures of the respiratory tract that involve incision or biopsy of the respiratory
mucosa
Procedures in patients with ongoing GI or GU tract infection
Procedures on infected skin, skin structure, or musculoskeletal tissue
Surgery to place prosthetic heart valves or prosthetic intravascular or intracardiac
materials.
Botulism: gram positive anaerobic rod, toxin
releasing, spore producing, with bioterrorism potential
The modern syndrome of botulism occurs in five forms, differentiated by the mode of
acquisition [2]:
 Food-borne botulism — ingestion of food contaminated by preformed botulinum toxin
 Infant botulism — the ingestion of clostridial spores that then colonize the host's
gastrointestinal (GI) tract and release toxin produced in vivo
 Wound botulism — infection of a wound by Clostridium botulinum with subsequent in
vivo production of neurotoxin
 Adult enteric infectious botulism or adult infectious botulism of unknown source —
similar to infant botulism in that toxin is produced in vivo in the GI tract of an infected
adult host.
 Inhalational botulism — the form that would occur if aerosolized toxin was released in
an act of bioterrorism.
• Cranial neuropathies, symmetric descending paralysis, no fever, no sensory loss
• The differential diagnosis for food-borne, wound, and adult enteric botulism includes:
•
•
myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), tick paralysis,
Guillain-Barré syndrome, poliomyelitis, stroke, and heavy metal intoxication. Less
likely diagnoses include tetrodotoxin and shellfish poisoning and antimicrobialassociated paralysis
Dx: clinical syndrome, EMG studies, reportable disease, stool studies, serum toxin
assays
Treatment: supportive (most need intubation), antitoxin (equine trivalent anti-toxin for
>1 year of age, botulism immunoglobulin for infants), PCN G for wound botulism
Giardia
 Flagellated protozoan parasite
 Cysts (live in environment), trophozoites (reproductive form)--
pear-shaped, binucleate, multi flagellated organisms,measures
9-15 µm long, 5-15 µm wide, and 2-4 µm thick
 Worldwide, food-borne, water-borne, person-person, especially
children in developing countries
 Other common GI parasite is Cryptosporidium parvum—Giardia
and Crypto problem in normal hosts and important in HIV and
immunocompromised (less common protozoan is E. histolytica)
 Dx: stool O and P (cyst and troph), stool antigenic testing
(ELISA)
Giardia trophozoite
Giardiasis
 60% asymptomatic
 Diarrhea that is sudden in onset and may be initially watery — 90










percent
Malaise — 85 percent
Foul-smelling and fatty stools (steatorrhea) — 70 percent
Abdominal cramps and bloating — 70 percent
Flatulence — 75 percent
Nausea — 70 percent
Weight loss — 65 percent
Vomiting — 30 percent
Fever— 10 percent
Manifestations often wax and wane over many months
Malabsorption—lactase (causes lactose intolerance), vitamin A,
B12, folate, etc
Miscellaneous
 Remember syphilis!!
 African tick fever—R. africae (look for eschars, early fever/myalgias)—





Amblyoma tick, doxycycline
Other tick borne diseases—R. rickettsia (dog tick, RMSF), Erlichia
(deertick—Ixodes or lone star tick), Borrelia (Lyme, Ixodes), Babesia
(protozoa looks like malaria, only in NE, fatal in asplenic pts, Ixodes)
Anthrax—cutaneous (Edema toxin), eschar; also inhalational
(hemorrhagic, widened mediastinum) and GI (ingestion of infected
animal)
Candidemia
Smallpox versus Chickenpox—degree of fever and early timing of
systemic symptoms, stage of lesions
Drugs:
 daptomycin contraindicated for MRSA pneumonia, follow CPK
 Linezolid—thrombocytopenia, bone marrow suppression, serotonin
syndrome
 HIV meds—abacavir (fatal hypersensitivity syndrome, HLA B5701),
protease inhibitors—elevated lipids, DM, nucleoside RTIs—
mitochondrial toxicity (lipodystrophy, visceral adiposity, myalgias,
neuropathy), nevirapine (fatal liver disease esp in women with high
CD4)
Thank You