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Clinical Microbiology ACOI Board Review 2018 gerald.blackburn@beaumont.org (No Disclosures)

Staphylococcal skin/soft tissue infection: abscess, rather than diffuse cellulitis, w/ purulent drainage common in diabetes Community-acquired (CA) MRSA more likely scenario body contact sports hx of spider bite

Rx of MSSA bacteremia? Nafcillin (side effect: AIN; dx: eosinophils in urine) Rx if non-anaphylactic rxn (rash) to PCN? Cephalosporin - cefazolin

Rx if MRSA (if susceptible)? Vancomycin Daptomycin (but NOT pneumonia) Linezolid (but NOT bacteremia) Trimethoprim/sulfa - especially SSTI Clindamycin - especially SSTI Quinolones (?) - not Cipro Rx of acute parotiditis (S. aureus most common); assoc. w/ surgery, dehydration, mouth breathing

Typical streptococcal SSTI (Grp A, B, G): Intense erythema (Often recurrent) cellulitis rather than abscess Lymphangitis Often (preceding) systemic symptoms Areas of pre-existent lymphedema, venous insufficiency Drainage, when present, often watery or serous

Erysipelas (superficial cellulitis of Streptococcal etiol.) Rx: penicillin if allergy: cephalosporin vancomycin clindamycin

Additional Streptococcal Syndromes: Viridans strep bacteremia - endocarditis S bovis/gallolyticus bacteremia - GI malignancy Grp A strep - necrotizing fasciitis flesh eating bacteria TSS - source usually obvious; often + blood culture (as can S. aureus - but.source often not obvious; blood cultures negative) Note:1/3 of Grp B strep are resistant to clindamycin (e.g. diabetic foot infection)

Necrotizing Soft Tissue Infections Group A strep: pain out of proportion to initial clinical findings Clostridium perfringens: progression over hours Mixed flora, most always including anaerobes Most commonly in diabetics; obesity Wounds involving/crossing mucous membranes Foul odor Mixed flora on gm stain Delayed or no growth on culture

Diabetic Foot Usually polymicrobial, w/ foul odor - Anaerobes Gm negatives Many feel pseudomonas commonly involved Rx (including pseudomonas coverage)?

Hx, Gm stain, speed of progression, location of wound, useful in predicting organism(s) Now what?

Huang C. N Engl J Med 2017;376:1158-1158.

C. perfringens gas gangrene Rx: Surgery + Penicillin + Clindamycin +? IVIG, HBO?

C. perfringens -> gas gangrene C. septicum bacteremia/sepsis GI/gyn malignancy (sometimes occult), chemotherapy-induced neutropenia C. botulinum -> skin popping w/ black tar heroin

Pasteurella multocida Rapid onset - painful, throbbing cellulitis gm neg rod RX: amoxicillin +/- clavulanate cefuroxime doxycycline quinolones NOT CEPHALEXIN (Keflex ) Cat Bite

Additional Pearls re: Bites Dog bites/splenectomy: overwhelming sepsis due to Capnocytophaga sp. (DF-2) Human bites: Eikenella - can t use clindamycin Snake bites: gm negs Rabies - any wild carnivore most common domestic animal? - cat Lagomorphs don t get rabies (exception: woodchucks)

Aeromonas hydrophila Gm neg rod Fresh water injuries, medicinal uses of leeches Rx: fluoroquinolone 3rd gen cephalosporin trimethoprim/sulfa

Working in yard: Dx? Tx? Nodular lymphangitis

D/D nodular lymphangitis Staph, strep Sporotrichosis: 1 lesion is painless Nocardia: 1 lesion is a tender ulceration M. marinum: 1 lesion is a tender papule Tularemia: 1 lesion is a painful ulceration, w/ systemic symptoms (classically associated w/ skinning rabbits)

Sporotrichosis: -minor trauma from roses or sphagnum moss -variable size yeast cells w/ multiple buds Tx: itraconazole

Mycobacterium marinum: cleaning fish tanks, water injuries, fish hooks, splinter from a boat Rx: Clarithromycin Doxycycline Minocycline Rifampin/ethambutol

Actinomycosis Spontaneous drainage from head ( lumpy jaw ), neck, or chest Often dental or oral mucosal origin Indolent, wooden mass effect; often confused w/ malignancy Assoc. w/ IUD s sulfur granules ->

Actinomyces: Gm + anaerobic, filamentous, beaded rods not acid fast (vs Nocardia: aerobic, weakly acid fast) Tx - prolonged course of: Ampicillin Doxycycline clindamycin

H. Zoster Type of isolation? Hutchinson s sign Ramsey Hunt syndrome (H. zoster oticus), involving facial nerve (VII), w/ facial palsy, otalgia, dermatomal vesicles, occasional hearing loss

Blastomycosis Mackowiak P A et al. Clin Infect Dis. 2012;55:1390-1391

Blastomycosis single, broad-based buds decaying vegetation, e.g. beaver dams Tx: Itraconazole often involves skin, bone; GU tract in males regardless of presentation, always considered as disseminated disease, w/ lungs being the primary entry site

Neutropenia/immunosuppression. including initial approach to the febrile neutropenic patient as well as the persistently febrile patient most common bacteremia: E. coli most lethal organism: pseudomonas - initial empiric rx always includes anti-pseudomonas coverage when remains febrile: antifungals

Ecthyma gangrenosum Most frequently assoc. w/ pseudomonas bacteremia Neutropenia, or other severely impaired immunity Erythematous / hemorrhagic pustule, evolving into central necrosis

Candida endophthalmitis severe neutropenia; may become apparent as neutrophils are recovering other setting/risk factors: ICU, multiple IVs/central lines, multiple antibiotics, TPN initial rx: echinocandins

Strongyloides: diffuse pulmonary infiltrates in an immunosuppressed host NOT grossly visible Rx: ivermectin / albendazole

CNS Presentations Neisseria meningitidis: acute meningitis w/ rash; Rx: ceftriaxone sepsis syndrome/bacteremia associated w/ terminal compliment deficiencies (C 5 - C 9 ), as well as splenectomy

Cryptococcus HIV+, other dx assoc. w/ t-cell deficiencies; sub-acute headache, mental status changes tx: amphotericin B + flucytosine / fluconazole

Additional potential CNS questions: Interpretation of CSF results in a patient with fever, CNS findings Bacterial, viral, fungal, TB Meningitis vs encephalitis HSV encephalitis Meningitis w/ highest mortality Complement deficiency Most common cause of lymphocyte-predominant meningitis in a young, otherwise healthy individual Listeria scenarios - who? CSF results, including gm stain w/ gm + rods? Rx?

D/D of Meningitis Bacterial Viral TB/Fungal Cell count increased; neutrophil predominant sl. increased; lymphocyte predominant increased; lymphocyte predominant Glucose decreased normal or sl. decrease decreased Protein elevated normal or minimally elevated elevated

N. gonorrhoeae gm neg intracellular diplococci painful urethral/cervical discharge pustular rash Late compliment deficiency Tx: cefixime (?) / ceftriaxone

Primary Syphilis: painless (usually genital) ulcer darkfield microscopy; PCR serology usually negative

Badri T, Ben Jennet S. N Engl J Med 2011;364:71-71. T. pallidum 2 stages and beyond -> dx by serology rash includes palms and soles RPR or VDRL to screen FTA as confirmatory (though being replaced by TP-PA)

Treatment of Syphilis Less than 1 yr s duration (includes primary, secondary and early latent): benzathine PCN 2.4 mill units i.m. x 1 If HIV +, some treat weekly x 3 Allergy: doxycycline, ceftriaxone Greater than 1 yr s duration (or unknown duration); late latent: benzathine PCN 2.4 mill units weekly x 3 Allergy: ceftriaxone, doxycycline

Treatment of Syphilis Neurosyphilis: 10-14 days IV PCN G, 18-24 mill. units/day If PCN allergic: desensitize or ceftriaxone probably effective In pregnancy, if PCN allergy - must densensitze (though ceftriaxone probably effective) Jarish-Herxheimer rxn

Malaria appropriate travel hx black water fever speciation by PCR at the CDC D/D Babesiosis Banana gametocyte: P. falciparum

Babesiosis (B. microti; B. divergens) Non-specific illness w/ headache, myalgia, malaise, fever after travel to coastal northeastern U.S. in late spring, early summer, particularly if hx of tick exposure 1-4 weeks earlier; much more severe illness if splenectomized Occasionally transmitted by transfusion Tick vector: Ixodes scapularis Reservoir host: white footed mouse Note: this same tick also transmits Lyme dx (Borrelia burgdorferi) and anaplasmosis. Consider if severe dx or poor response to treatment for these other diseases

Babesiosis* Hemolytic anemia, thrombocytopenia No rash Dx: RBC inclusion bodies ~ malaria on blood smear; however, tetrads ( Maltese cross formations ) NOT seen in malaria Dx: PCR Rx: atovaquone + azithromycin if mild; IV clindamycin + p.o. quinine +/- exchange transfusion if severe *Vannier & Krause. NEJM 2012;366: 2397-2407

Babesiosis Noskoviak K, Broome E. N Engl J Med 2008;358:e19.

Lyme Disease (Borrelia burgdorferi) Erythema migrans

Lyme Disease > 300,000 cases/yr in U.S. Systemic symptoms, rash, joint, CNS involvement erythema migrans > 90% carditis w/ conduction defects <10% various neurologic presentations ~15% cranial neuropathies; esp. bilateral VII nerve palsey; meningitis; radiculopathy IF chronic disease exists, may be due to immune dysregulation (elevated IL-23 and/or other) Prophylaxis: 200mg doxycycline x 1

Ehrlichiosis/Anaplasmosis Human Monocytic Ehrlichiosis: E. chaffeensis Monocytes macrophages of liver, spleen and bone marrow S.E, south-central, mid-atlantic U.S. Human Granulocytic Anaplasmosis: Anaplasma phagocytophilum seen on peripheral smear (granulocytes) upper-midwest, N.E., California, Europe E. ewingii: as above except geography of HME

Ehrlichiosis/Anaplasmosis: following tick exposure flu-like illness w/ leukopenia, thrombocytopenia spring/summer hyponatremia, elevated LFT s Note: morulae - cytoplasmic inclusions of elementary bodies Common only w/ anaplasma Diagnosis by PCR, blood smear Tx: doxycycline

Treatment Warning: Questions about treatment failure Lyme Dx: Amoxicillin/cefuroxime Ceftriaxone Doxycycline Ehrlichiosis/Anaplasmosis: Doxycycline Babesiosis: Atovaquone + azithromycin

Esfandbod M, Malekpour M. N Engl J Med 2009;361:178-178. Cutaneous anthrax systemically ill painless eschar w/ marked, localized edema contaminated soil, livestock

Bioterrorism-related Anthrax Multiple, previously healthy pts, w/ severe, rapidly fatal, flu-like illness pneumonia uncommon Widened mediastinum Large hemorrhagic pleural effusions Hemorrhagic meningitis Tx: penicillin / ciprofloxicin / doxycycline

CSF Gm stain - Anthrax (JAMA; 2001)

Severe illness w/ painful, nodular rash Severe back pain Smallpox All lesions in the same stage Rash most prominent on face and extremities, including palms and soles