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Infectious Diseases for the Medicine Boards

Infectious Diseases for the Medicine Boards. Christopher Hurt, MD Division of Infectious Diseases June 2010. What is sure to be on the boards. ABIM Exam Blueprint, http://www.abim.org/pdf/blueprint/im_cert.pdf. What may be on the boards.

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Infectious Diseases for the Medicine Boards

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  1. Infectious Diseases for the Medicine Boards Christopher Hurt, MD Division of Infectious Diseases June 2010

  2. What is sure to be on the boards ABIM Exam Blueprint, http://www.abim.org/pdf/blueprint/im_cert.pdf

  3. What may be on the boards ABIM Exam Blueprint, http://www.abim.org/pdf/blueprint/im_cert.pdf

  4. What won’t be on the boards • Dosages of antimicrobials • Emerging pathogens • 2009 H1N1 unlikely, but oseltamivir-resistant flu A could be • Topics that are controversial or which have no consensus guideline, such as… • Treatment of multidrug-resistant TB or HIV • Probably won’t ask you for second- or third-line antimicrobial selections • (that’s special torture reserved for ID boards) • Bioterrorism ± • (at least recognize wide mediastinum of inhalation anthrax)

  5. Let’s go!

  6. Critical care ID - 1 • SIRS = 2 or more of: fever or hypotherm; tachycardia; tachypnea/hypocarbia; leukocytosis or leukopenia • NOT necessarily due to an infection • Sepsis = SIRS plus micro-confirmed or observable infxn • Severe sepsis = sepsis plus at least one sign of organ hypoperfusion • Mottled skin, delayed cap refill, decr UOP, lactatemia, AMS, abnl EEG, thrombocyto, DIC, ALI/ARDS, cardiac dysfunction • Septic shock = severe sepsis plus low MAP and/or pressor requirement

  7. Critical care ID - 2 • Drotrecogin alpha (Xigris) • PROWESS = 96h infusion w/in 24h of presenting • 28d mortality rate lower with drotrecogin • Increased bleeding with drotrecogin • Post-hoc analysis = of greatest benefit to most severely ill, with APACHE II scores ≥25 or MSOF • Lower incidence of MSOF among treated patients, and they also had more rapid recovery of cardiopulm function

  8. Critical care ID - 3 • Who should NOT get drotrecogin alpha (Xigris) • Preggers or breast-feeding • Severe thrombocytopenia (<30K) • ANY invasive procedure within 12h of starting drug • Spinal epidural anaesthesia is a favorite trivia bit • Head trauma, intracranial surg, or CVA w/in 3mos • Known hypercoagulable condition • Patient not expected to live 28d post-infusion • Acute pancreatitis with no identified source of infxn

  9. Critical care ID - 4 • Lines and bloodstream infections (BSIs) • Yank all intravascular catheters as soon as feasible • Dirtiness: femoral > IJ (drool!) > SCL • If the line is okay, leave the damn thing alone – no evidence that scheduled (q3-5d) line changes help reduce nosocomial BSIs • For site prep, use chlorhexidine gluconate (CHG) over povidone/iodine (Betadine), if given a choice

  10. CNS Infections - 1 • Meningitis = pain, headache, lethargy, function OK • Aseptic (viral or non-infectious) or bacterial • Encephalitis = brain abnormalities • Hemiparesis, AMS, flaccid paralysis, paraesthesias • Distinctions usu based on CSF – viral dzs have lower WBC counts, only modest protein elev, near-normal glucose • Don’t hang your hat on lymphs vs PMNs to help! You can see lymphs in early or partially tx’d bacterial meningitis • Meningoencephalitis = elements of both syndromes

  11. CNS Infections - 2 • Encephalitis • Viral ~ = neuronal involvement by MRI • Measles, VZV, CMV, influenza, arboviruses • HSV-1 is responsible for most deaths in encephalitis • West Nile is like polio or Guillain-Barré – flaccid ascending paralysis • Post-infectious aka acute dissem. encephalomyelitis (ADEM) = neuronal sparing, perivascular inflamm w/ demyelination (often an incidentaloma on MRI)

  12. CNS Infections - 3 Meningitis – Viral and Noninfectious • Viral – enteroviruses, HSV, HIV, WNV, VZV, mumps • PCR is diagnostic tool, esp for entero and HSV/VZV • Acute HIV can present with mono-like illness + meningitis • HSV more likely culprit if pt presenting with 1° genital lesion • Recurrent HSV-2 associated meningitis episodes = Mollaret’s • Other bugs = RMSF (Rickettsia), Ehrlichia, Lyme (Borrelia) • Non-infectious causes • Malignancy (breast, lung, melanoma, GI, unk primaries) • Drug-induced (NSAIDs, TMP/SMX, IVIG, OKT3 – immsupp)

  13. CNS Infections - 4 Meningitis – Bacterial • Access CNS either through contiguous spread (e.g., parameningeal focus, sinus/middle ear) or hematogenous • Bugs in adult bacterial meningitis (up to age 60) • Streptococcus pneumoniae – 60% • Neisseria meningitidis – 20% • Haemophilus influenzae – 10% • Listeria monocytogenes – 6% • Group B Streptococcus (agalactiae) – 4% • Over age 60, 70% S.pneumo and 20% Listeria

  14. CNS Infections - 5 Meningitis – Bacterial • Listeriosis has more seizures and focal neuro deficits, presenting as rhomboencephalitis (ataxia, CN palsies, nystagmus) – think this in an elderly meningitis vignette • Gram stain buzzwords • Gram-positive, lancet-shaped diplococci = S.pneumo • Gram-negative diplococci = N.meningitidis (meningococcus) • Gram-negative coccobacilli = H.flu • Gram-positive rods or coccobacilli = Listeria

  15. CNS Infections - 6 Meningitis – Bacterial – TREATMENT • DO NOT DELAY – if the Q frames pt languishing in ER for hours before you see him, give abx before doing the LP • Look for papilledema in lieu of getting a head CT • If ß-lactam is an option, use it – cidal, penetrates the BBB • Empirical therapy = hi-dose ceftriaxone + vancomycin • Ceftriax 2gm q12 = meningococcus & PCN-sensitive S.pneumo • Vancomycin = PCN-resistant S.pneumo • IF OVER AGE 50, add ampicillin (±gent) for Listeria • Only scenario for adjunctive dexamethasone is highly suspected (or confirmed) pneumococcalmeningitis

  16. CNS Infections - 7 • Rhinocerebral zygomycosis not “mucormycosis” • Hyperglycemic diabetic patient in HHS/HONK or DKA • Acute sinusitis with fever, purulent nasal d/c, HA • Periorbital or facial swelling ± proptosis • Invasion of cavernous sinus leads to CN palsies (6&3, 4/5) • Rhizopus spp. are most common culprits • Not everyone’s favorite go-to fungus, Aspergillus • These fungi are vaso-invasive, so on PEx you may see black mucosal patches – it’s not the mould you’re seeing, it’s infarcted tissue • Treatment is with surgery FIRST and adjunctive amphoB

  17. Endocarditis - 1 • 2007 Modified Duke criteria: 1 major + 1 minor, or 3 minors

  18. Endocarditis – 2 • Indications for surgical intervention in IE • Vegetations: persistent after systemic embolization, anterior mitral leaflet veggies, ≥embolic events in first 2 weeks of abx, increase in veggie size despite abx • Valvular dysfunction: acute AI or MR with signs of ventricular failure, CHF unresponsive to medical tx, valve rupture • Perivalvular extension: valvular dehiscence/rupture/fistula, new heart block, large abscess

  19. Endocarditis – 3 Native valves • PCN-susceptible Viridans streptococci and S. bovisMIC≤0.12 • Penicillin G or ceftriaxone, or vanc x 4 wks • PenG or ceftriaxone PLUS gentamicin x 2 wks (synergy) • PCN-intermediate Viridans strep and S. bovisMIC>0.12, ≤0.5 • PenG or ceftriaxone x 4 wks with gent for FIRST 2 wks • Vanc x 4 wks • Staphylococcus aureus • NafcillinOSSA, oxacillinOSSA, or vancomycinORSA x 6 wks • Enterococcus – gentamicin ENTIRE TIME • Amp + gent x 4-6 wks, vanc + gent x 4-6 wks

  20. Endocarditis – 4 Prosthetic valves • PCN-susceptible Viridans streptococci and S. bovisMIC≤0.12 • Penicillin G or ceftriaxone, x 6 wks, ± gent x FIRST 2 • Vanc x 6 wks • PCN-int or resistant Viridans strep and S. bovisMIC>0.12 • PenG or ceftriaxone x 6 wks with gent for all 6 wks • Vanc x 6 wks • Staphylococcus aureus • Naf/oxOSSAor vancORSAPLUS rifampin x ≥6 wks, w/gent FIRST 2 • Enterococcus – gentamicin ENTIRE TIME • Amp + gent x 6 wks, vanc + gent x 6 wks

  21. Endocarditis – 5 TAKE-HOME MESSAGES FOR ENDOCARDITIS • Don’t memorize the Duke criteria – it’s intuitive • Gentamicin shortens the course for “weak” bugs (Low-PCN MIC Viridans group strep and S.bovis) • If Enterococcus is present, must use gent entire course • Prosthetic valve treatment is always 6 wks, sometimes with adjunctive abx (e.g., rifampin, gent) depending on bug • Staphylococcustreatment is always 6 wks

  22. Intravascular infections – 1 • Staphylococcus aureus and Salmonellaare associated with vascular (esp aortic) aneurysms • Think about this dx if high-grade (persistent) bacteremia in pt without endovascular material • Syphilis (Treponema pallidum) was once a major cause of aortitis – late presentation of dz • Thoracic aortic dilatation with aortic regurgitation

  23. Intravascular infections – 2 • Rocky Mountain spotted fever • Southeastern US (“tick belt” from Arkansas – NC – FL) • Rickettsia ricketsii attach to vascular endothelium = leak • Fever, severe HA, rash in 90% (beware pts of color!), myalgias, focal neuro signs, thrombocyto, ARF, hypoNa • Doxycycline ASAP – treat empirically; no good acute dx tool

  24. Lower respiratory tract infections - 1 Community-Acquired Pneumonia • Bugs: Strep pneumo, Mycoplasma pneumoniae, H.flu, Chlamhydophila pneumoniae, respiratory viruses, Legionella • Outpatient tx • Previously healthy, no abx w/in 3 mos? Macrolide or doxy • Comorbidities? Respiratory FQ OR [ß-lactam + macrolide] • Inpatient, non-ICU – resp FQ OR [ß-lactam + macrolide] • Inpatient, ICU – ß-lactam PLUS [resp FQ or azithro] • ß-lactam choices: cefotaxime, ceftriaxone, amp/sulbactam • Pseudomonas? pip/tazo, cefepime, imi/mero ± aminoglycoside • MRSA/ORSA? ADD vancomycin or linezolid

  25. Lower respiratory tract infections - 2 Healthcare and Ventilator-Acquired Pneumonias • Bugs: Pseudomonas, E.coli, Klebsiella, Acinetobacter, S.aureus • Increased risk for multidrug resistant (MDR) bugs? • Abx w/in 90d, current hospitalization ≥5d, high-freq of abx resistance in unit, risk factor for HCAP (hospitalization x2d in prior 90d, nursing home resident, home infusion, dialysis, close contact) • HAP/VAP if no known risk factors for MDR-bug (realistically, very rare) • Ceftriaxone or levoflox/moxi or amp/sulbactam or ertapenem • High risk for MDR-organisms or presenting with late-onset dz • Antipseudomonal ß-lactam: cefepime, ceftaz, imi, mero, or pip/tazo AND cipro, levo, amikacin, gent, or tobra • If MRSA concern, ADD linezolid or vancomycin NOT daptomycin

  26. Lower respiratory tract infections - 3 • BMT and SOT recipients • Nocardia spp. – if in lung, think of brain, too! • Beaded, branching, filamentous bacteria, ± acid-fast • Incidence has dropped due to TMP/SMX prophy use post-xp • TMP/SMX or imipenem empirical tx, awaiting susceptibilities • Get a CT of the head looking for ring-enhancing lesions • Aspergillus spp. • Marijuana smoking post-xp is a risk factor • “Crescent sign” on chest CT is buzzword • Vasoinvasive and tissue destructive • AmphoB, echinocandin (caspo/mica/anidula), or vori/posa

  27. Lower respiratory tract infections - 4 • Pneumocystis jiroveci (still called PCP) • CD4 ≤ 200-250 • HIV and transplant pts + fludarabine (CD4-penic) • Nonproductive cough, fever, insidious SOB • Steroids if PaO2 <70 • Tx = IV TMP/SMX orIV pentamidine* *Inhaled only for prophy

  28. Lower respiratory tract infections - 5 • Mycobacterium tuberculosis • TST/PPD is a crappy test, but don’t use “anergy” panel • KNOW THE THRESHOLDS FOR POSITIVE TST/PPD!!!

  29. Lower respiratory tract infections - 6 • Mycobacterium tuberculosis • Treatment always initiated with four drug “RIPE” regimen, at weight-based dosing • Isoniazid – hepatotoxicity, anion gap acidosis (I in MUDPILES) • Rifampin – inducer of metabolism of other drugs, orange body fluids, hepatotoxicity • Ethambutol – optic neuritis (color blindness) • Pyrazinamide – hepatotoxicity, nausea-inducing • Pulmonary TB: total of 6 months treatment ALL ON DOT • First 8 weeks on RIPE – if fully susceptible and smear negative at 2 month recheck, then OK to narrow to just INH + Rifampin

  30. Lower respiratory tract infections - 7 • Histoplasma, Coccidioides, Cryptococcus • All gain entry through inhalation, then disseminate • Histoplasma – Mississippi-Ohio River Valley, interstitial pneumonia, mucocutaneous ulcers, splenomegaly, marrow suppression, fibrosing mediastinitis, “coin” lesion in HIV– • Coccidioides – Desert SW (Mexican immigrants and eco-tourists), hilar adenopathy, arthralgias, erythema nodosum (can be mistaken for sarcoidosis) • Cryptococcus – pneumonitis is usually subclinical, may have cryptococcomas of lung, can be normal hosts but if compromised (HIV, steroids, transplant) need LP

  31. Enteric infections - 1 • Norovirus • Rapid-onset explosive outbreak with quick resolution • Child exposures, cruise ships, congregate living facilities • Low infectious inoculum, highly transmissible • Vomiting precedes abd cramping, fever (<50%), watery diarrhea, constitutional sxs (HA, chills, myalgias) x 2-3d • Can cause deaths among the elderly • Treatment = oral rehydration, supportive care • Antimotility and antisecretory drugs are okay to use

  32. Enteric infections - 2 • Dysentery = bloody stools; 4 main causes in US… • Shiga toxin-producing E.coli (60% are O157:H7) • Watery diarrhea becomes bloody in 1-5d; abd cramps, no fever • Causes hemolytic-uremic syndrome if toxin reaches kidneys • Shigella (outbreaks uncommon; more in developing world) • Campylobacter – poultry, unpasteurized milk; Guillain-Barré • Non-typhoid Salmonella – poultry, pet reptiles and turtles • Treatments • Shiga toxin-producing E.coli – Abx not recommended • Shigellosis, salmonellosis – ciproflox, levoflox, azithro • Campylobacter jejuni – azithro

  33. Enteric infections - 3 • Clostridium difficile diarrhea • Toxin assay for diagnosis, but don’t attempt test-of-cure • Initial episode, mild-to-moderate • Metronidazole 500mg PO (not IV) q8h x10-14d • Initial episode, severe (WBC ≥15, Cr ≥1.5x premorbid level) • Vancomycin 125mg PO (not IV) q6h x 10-14d • Initial episode, severe and complicated by shock, megacolon • Vancomycin 500mg PO or pNGT PLUS metronidazole 500 q8 • If complete ileus, consideration for intrarectal vancomycin • First recurrence = same as initial episode • Second recurrence = vancomycin taper

  34. HIV and AIDS - 1 • HIV-1 predominates • HIV-2 limited to W. Africa • ssRNA retrovirus • AIDS is defined by: • CD4 < 200 cells/µL • CD4% < 14% • Presence of AIDS-definingillness at any CD4

  35. HIV and AIDS - 2 • ELISA = highly sensitive • Better to have FP than miss a TP! • Western blot = highly specific • Indeterminate Western blots arerare… but can be caused by: • Neoplasms, dialysis, thyroid dz,bilirubinemia, SLE, pregnancy,immunizations (tetanus, HIV)nephrotic-range proteinuria

  36. HIV and AIDS - 3 • Acute retroviral syndrome isa mononucleosis-like illness • Fever • Maculopapular rashThink syphilis, too! • Mucocutaneous ulcers • Pharyngitis ± tonsillar enlargement • Lymphadenopathy • Meningitis (infrequent) • DIAGNOSIS OF ACUTE HIV IS BY RNA, NOT Ab!!!

  37. HIV and AIDS - 4 Initial mgm’t – Prophylaxis • CD4 > 200, no prophylaxis necessary • CD4 < 200 • Pneumocystis jiroveci and Toxoplasmosis • TMP/SMX > dapsone > atovaquone • Aerosolized pentamidine prevents ONLY Pneumocystis • Do NOT need fluconazole for thrush “prophylaxis” • CD4 < 50 • Mycobacterium avium complex (“MAI” doesn’t exist!) • Azithromycin 1200mg once weekly

  38. HIV and AIDS - 5 Initial mgm’t – Antiretrovirals • For CD4 < 200 or if AIDS-defining illness, everyone should get on ARVs • Recent (2009, so NOT on boards yet) evidence suggests starting ARVs during some acute OIs reduces mortality • For now, ABIM would say to start after stabilization, etc. • Btw 200-350, recommended to start • Over 350, decision btw pt and provider

  39. HIV and AIDS - 6 Initial mgm’t – Antiretrovirals • Current testable recommendations are probably slightly out-of-date (circa 2008); field moving rapidly

  40. HIV and AIDS - 7 • Cryptococcal meningitis • Malaise, headache, N/V, low-grade fevers, without much meningismus or AMS • Think of dx also in ALL, Hodgkin’s, or recent steroid use • Get serum crypto Ag – India ink is rarely used • Morbidity/mortality comes from increased ICP, so get opening pressure on LP and perform serial LPs • Can also place lumbar drain or ventricular drain, if needed • Amphotericin B + flucytosine x14d for CNS disease • THEN switch to oral fluconazole and stay on it until CD4 > 200

  41. HIV and AIDS - 8 Antiretroviral side effects • ddI, d4T/stavudine, AZT/zidovudineNRTIs - lactic acidosis • TenofovirNRTI - Fanconi-like syndrome w/“creatinine creep” • AbacavirNRTI – hypersensitivity rxn (if HLA B*5701 present) • EfavirenzNNRTI - teratogenic, causes vivid dreams • NevirapineNNRTI - hepatotoxic if started with high CD4s, SO AVOID USING NEVIRAPINE IN PEP REGIMENS • IndinavirPI - nephrolithiasis • RitonavirPI - “booster” agent, tons of drug-drug interactions • AtazanavirPI - Gilbert-like syndrome of hyperbili ± jaundice

  42. Antimicrobial adverse effects • Sulfa drugs – rash, AIN/ARF, kernicterus in neonates • TMP – hyperkalemia (decr renal tubular excretion) • ß-lactams – marrow, seizures, AIN/ARF • Daptomycin – rhabdomyolysis • Metronidazole – disulfiram-like reaction with EtOH • Oxacillin – hepatitis/transaminitis • Pentamidine – pancreatitis, hypoglycemia • Amphotericin – renal failure, rigors (meperidine) • Vancomycin – “red man” (histamine release), nephro/ototox (??) • Aminoglycosides –ototoxicity, c/i in myasthenia gravis • Linezolid – marrow toxicity, MAOI activity (serotonin syndrome)

  43. Infectious/septic arthritis - 1 • Diagnosis • Arthrocentesis to eval for crystalline arthropathy • Generally >50K cells/µL as threshold for septic joint • Look for Gram-positives… #1 cause is S.aureus, followed by streptococci

  44. Infectious/septic arthritis - 2 Monoarticular joint presentations • Late Lyme arthritis (Borrelia burgdorferi) • Knee > shoulder > ankle > elbow > TMJ > wrist > hip • Effusion is greater than the pain • Fluid can meet WBC criteria for septic joint, but uncommon • Diagnosis relies on serologies • Gonorrhea • Triad of migratory polyarthralgia, dermatologic lesions (macules, papules/pustules), tenosynovitis • Dx is by confirming genital or extragenital GC infection

  45. STIs and GU tract infections - 1 • Gonorrhea (Neisseria gonorrhoeae) • Gram-negative intracellular diplococcus • Purulent urethritis or cervicitis • Most cases resolve spontaneously – treat to prevent disseminated gonococcal infection (DGI) • Fevers, asymmetric mono/oligoarticular arthritis (knee, ankle) or • Tenosynovitis- muscle pain; overlying papules w/hemorrhage • Uncomplicated GU dz = IM ceftriaxone or PO cefixime, x1 • Extragenital dz or DGI = IM ceftriaxone, x1 • ALWAYS co-treat for Chlamydia with 1gm azithro, x1 • NEVER use a quinolone for an STI on the boards!

  46. STIs and GU tract infections - 2 • Chlamydia trachomatis (and the catch-all, NGU) • Includes Ureaplasma urealyticum, Mycoplasma genitalium • Incubation period is longer for CT (1-4wks) than GC (2-6d) • Clear (non-purulent) discharge; Gm stain = WBC, no bugs • Treat with 1gm azithromycin PO, x1 or doxy 100 q12 x7d • Pelvic inflammatory disease • Can be from GC or CT, sometimes vaginal anaerobes • Fitz-Hugh-Curtis = purulent perihepatitis with mild LFT chgs • If pregnant, must admit the patient • Tx w/ceftriaxone x1, doxy and metronidazole x14d

  47. STIs and GU tract infections - 3 • Syphilis – RPRnon-treponemal, confirmtreponemal = MHA-TP, TP-PA • 1° = painless chancre, ~21d after contact, lasting ~3-6 wks • 2° = non-pruritic skin rash and mucous membrane lesions • Rough, red or brownish spots on trunk, palms and soles • Systemic symptoms with fever, LAD, sore throat, hair loss • Syphilitic hepatitis (1° & 2°) = cholestatic, but alk phos >> bili • Latent – seroreactivity without e/o disease • Early latent – if acquired syphilis within the prior year • Late latent – unknown acquisition date • 3°/Late – evidence of end-organ damage – PCN x 3 wks • Neurosyphilis – IV PCN x14d, desensitize in ICU if needed PCN x1 PCN x1 PCN x1 PCN x3 wks

  48. STIs and GU tract infections - 4 • Herpes • Painful ulcerations of genital mucosa, usually from HSV-2 • Remember primary genital lesion assoc w/ HSV meningitis • First episode: ACV, famciclovir, or vACV x 7-10d • Suppressive therapy does reduce viral shedding and prevent recurrent episodes • ACV 400 q12, famciclovir 250 q12, or vACV 500 q24

  49. STIs and GU tract infections - 5 • Trichomoniasis • If it’s moving fast on a wet prep, it’s Trichomonas vaginalis • Frothy, thin, foul-smelling d/c for women; men often w/o sxs • Kill it with metronidazole 2gm po, x1 unless pregnant, then use metronidazole 500 q12h x7d. AVOID EtOH (disulfiram) • Bacterial vaginosis – NOT an STI • “Salt-and-pepper” covered clue cell • Fishy odor, pH > 5.0 • Metro 500 q12h x7d Clue cells Normal

  50. Hepatic infections - 1 • Hepatitis B • dsDNA virus • Blood and body fluidsare source • Majority (95%) of normal hostswill clear virus • Strong assoc w/HCC,esp among Asians whowere vertically infected

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