ID BOARD REVIEW 2009

1. ID BOARD REVIEW 2009 Amanda Peppercorn, M.D. Assistant Professor of Medicine University of North Carolina at Chapel Hill

2. 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

3. Desquamation

4. 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)

5. 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

6. 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

7. 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

8. 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

10. 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, conferring resistance to all penicillin and cephalosporin family of antibiotics WTA=wall teichoic acid; PVL=Panton-Valentine leukocidin; CHIP=chemotaxis inhibitory protein. Zetola N et al. Lancet Infect Dis. 2005;5:275-286. Deresinski S. Clin Infect Dis. 2005;40:562-573. Foster TJ. J Clin Invest. 2004;114:1693-1696.

11. COMPARISON:CA-MRSA AND HA-MRSA Diederen BMW, et al. JID 2006;52:157-168

13. 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

14. 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

15. Palmar involvement—secondary syphilis

16. Labial Condyloma Lata, Secondary Syphilis

17. CDC ISOLATION GUIDELINES Isolation Precautions • Standard precautions • Airborne precautions • Special airborne precautions • Droplet precautions • Contact precautions • Protective precautions

18. 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

19. AIRBORNE PRECAUTIONS Isolation • Private negative pressure room • Direct out exhausted air • N95 respirator Representative pathogens • M. tuberculosis • Varicella, Zoster (immunocompromised) • Measles

20. SPECIAL AIRBORNE PRECAUTIONS Isolation • Airborne + eye shields Representative pathogens • Avian influenza • Monkeypox • SARS Co-V • Smallpox • Viral hemorrhagic fever (e.g., Ebola, Lassa)

21. DROPLET PRECAUTIONS Isolation • Private room • Mask Representative pathogens • Invasive N. meningitidis • RSV • Bordetella pertussis • Rubella, Mumps • Group A streptococcal pharyngitis • Invasive H. influenzae

22. CONTACT PRECAUTIONS Isolation • Gloves • Gowns Representative pathogens • Clostridium difficile • HSV • Varicella/zoster • VRE, MRSA • MDR pathogens (resistant to two or more classes of pathogens)

23. 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)

24. 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

25. POST-EXPOSURE PROPHYLAXISUSING 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

26. 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)

27. NO POST-EXPOSURE PROPHYLAXIS • Adenovirus conjunctivitis • Hepatitis C • Mumps • Parvovirus B19 • Rubella • Severe acute respiratory distress syndrome (SARS)

28. PATHOGENS ASSOCIATED WITH SKIN AND SOFT TISSUE INFECTIONS

29. PATHOGENS ASSOCIATED WITH SKIN AND SOFT TISSUE INFECTIONS

30. 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

31. BOARD REVIEW QUESTIONS:SKIN • #68 – Osteo in drug user • #71 – Human bite • #83 – Cat bite • #85 – IDU joint infection • #94 – SA infection • #107 - NTM

32. CAP: PATHOGENS *Influenza A and B, adenovirus, RSV, parainfluenza Mandell LA, et al. Clin Infect Dis 2007;44(suppl 2):27-72

34. 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 amox-clav} • Regions with >25% high level macrolide resistant SPn use alternative agent

35. 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

36. 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 [TMP-SMX]) • 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

37. 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.

38. 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)

39. 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

40. 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

41. 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.

42. 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

43. 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.

44. 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 antimicrobial-associated 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

45. 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)

46. Giardia trophozoite

47. 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

48. 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)

49. Thank You