Infectious Disease System
Infectious Disease
High-yield infectious disease for USMLE Step 1/2/3 — fungal infections, septic arthritis, osteomyelitis, herpes viruses, travel medicine, and antibiotic selection organized by exam-actionable clusters with full treatment tables and clinical reasoning frameworks.
By Dr. Marish Asudani · Published · Updated
Which Divine Intervention infectious disease episodes are high-yield for Step 2?
This guide covers 7 Divine Intervention infectious disease episodes plus 5 Rapid Review episodes for Step 1/2/3, in 4 clusters: HIV & Opportunistic Infections, Systemic Bacterial Infections, Vector-borne & Tropical, and Antimicrobial Stewardship. The NBMEs now give immunosuppression via steroids, transplant or diabetes and expect you to recognize the same organisms, so learn CD4 thresholds, prophylaxis drugs and treatment drugs as 3 distinct memory banks. Septic arthritis, osteomyelitis, travel medicine and antibiotic selection are covered too.
HIV/AIDS & Opportunistic Infections
The NBMEs have evolved away from the obvious HIV-OI pairing. They now give immunosuppression via steroids, transplant, or diabetes and expect you to recognize the same organisms. Master CD4 thresholds, prophylaxis drugs, and treatment drugs as three distinct memory banks — the exam tests all three independently.
EP352
The Clutch Fungi Podcast
- Pneumocystis jirovecii (PCP): CD4 <200 → prophylax with TMP-SMX or dapsone or pentamidine. Treatment: TMP-SMX ± prednisone (if PaO₂ <70 or A-a gradient ≥35). Silver stain (methenamine silver) on BAL. Associated with SIADH → hyponatremia.
- Cryptococcus neoformans: Most common meningitis in HIV. India ink stain → encapsulated yeast. CSF: ↑ lymphocytes, ↓ glucose, ↑ opening pressure. Treatment: amphotericin B + flucytosine → then fluconazole ×9–12 months maintenance.
- Candida spectrum: Intertrigo (obese/diabetic), esophagitis (HIV or inhaled steroid users), vulvovaginitis (pH ≤4.5, pseudohyphae on wet prep). Disseminated → echinocandin (caspofungin/micafungin) or amphotericin B — NOT azoles.
- Aspergillus fumigatus: Septate hyphae branching at 45°; catalase-positive. Aspergilloma in old TB cavities (eosinophilia; surgery + no antifungals). ABPA in CF/asthma (eosinophilia + IgE ↑ + bronchiectasis → steroids). Invasive: voriconazole or posaconazole (first-line), amphotericin B (second-line).
- Mucormycosis: Rhizopus sp. in DKA or neutropenic patient. Necrotic facial lesion, epistaxis, rhinosinusitis. Surgical emergency: debride + amphotericin B.
- Geographic fungi: Histo (Ohio/Kentucky valley; treat itraconazole; prophylax if CD4 <150), Cocci (SW US/earthquake; treat fluconazole; prophylax if CD4 <250), Blasto (Michigan/Ontario; broad-based budding yeast; itraconazole). All three respond to itraconazole.
CD4 Count Thresholds — Prophylaxis Master Table
| CD4 Threshold | Organism | Prophylaxis Drug |
|---|---|---|
| <200 | Pneumocystis jirovecii (PCP) | TMP-SMX (1st); dapsone or pentamidine if sulfa allergy |
| <100 | Toxoplasma gondii | TMP-SMX (same drug — double benefit) |
| <150 | Histoplasma (if endemic) | Itraconazole |
| <250 | Coccidioides (if endemic) | Fluconazole |
| <50 | MAC (Mycobacterium avium complex) | Azithromycin |
Fungal Treatment Quick Reference
| Fungus | 1st-Line Rx | Key Side Effects / Notes |
|---|---|---|
| PCP (Pneumocystis) | TMP-SMX | G6PD deficiency → hemolytic anemia (sulfur oxidant). Add prednisone if PaO₂ <70. |
| Cryptococcus meningitis | Amphotericin B + flucytosine | Then fluconazole × 9–12 months. High opening pressure → serial LP. |
| Invasive Candida | Echinocandin (caspofungin) | Inhibit 1,3-β-D-glucan synthase. Remove lines. Do NOT use azoles for disseminated disease. |
| Invasive Aspergillus | Voriconazole / posaconazole | Second-line: amphotericin B. Visual changes common with voriconazole. |
| Mucormycosis | Surgical debridement + amphotericin B | Control DKA immediately. High mortality without surgery. |
| Sporothrix schenckii | Itraconazole | Rose gardeners / thorn prick. Lymphangitis in linear distribution (ascending arm). KI (potassium iodide) for cutaneous only. |
| Tinea / Dermatophytes | Topical azole (most) | Onychomycosis / tinea capitis → systemic: terbinafine or griseofulvin. Griseofulvin = CYP450 inducer. |
| Tinea versicolor | Topical azole | Malassezia furfur. Spaghetti and meatballs on KOH. Inactivates tyrosinase → hypopigmentation. |
Classic Trap — PCP Beyond HIV
PCP pneumonia occurs in ANY chronically immunosuppressed patient: organ transplant recipients, chronic steroid users (e.g., persistent asthma on prednisone), TNF-inhibitor therapy. Bilateral interstitial/ground-glass infiltrates + hyponatremia (SIADH) = trigger to think PCP regardless of HIV status.
Aspergilloma vs ABPA vs Invasive Aspergillosis
Aspergilloma: Old TB cavity + hemoptysis + eosinophilia. No antifungals; surgery if needed.
ABPA: Asthma/CF + very high IgE + bronchiectasis + eosinophilia → steroids (primary) ± itraconazole.
Invasive: Severe neutropenia → voriconazole/posaconazole. Lung nodules with halo sign on CT.
Aflatoxin Integration
Aspergillus flavus/parasiticus produce aflatoxins (found in moldy peanuts/grains) → hepatocellular carcinoma. Tumor marker: AFP (also elevated in yolk sac tumor and hepatoblastoma — all three are the HY AFP triad).
EP627
The Clutch Herpes Podcast — Part B (HHV-2 through HHV-8)
- HSV-2: Latent in sacral ganglion (not trigeminal). Causes meningitis more than encephalitis (opposite of HSV-1 which causes temporal lobe encephalitis). Neonatal herpes = HSV-2. PCR of CSF = diagnostic gold standard. Hemorrhagic CSF = classic.
- VZV (HHV-3): Latent in dorsal root ganglion or trigeminal ganglion. Chickenpox → shingles. Herpes zoster ophthalmicus = V1 branch of CN5. Vaccine is live attenuated → avoid if CD4 <200, pregnancy, immunodeficiency. Most common complication = post-herpetic neuralgia (PHN) → treat with gabapentin/pregabalin, TCAs, or SNRIs (avoid TCAs in elderly due to anti-HAM effects).
- EBV (HHV-4): Infects B cells via CD21. Mono = posterior cervical LAD + splenomegaly + atypical T cells (Downy cells) + heterophile antibody positive. Amoxicillin rash = NOT a penicillin allergy (patient can retake amoxicillin). Avoid contact sports × 4 weeks (splenic rupture). EBV malignancies: Burkitt's (t8;14, starry sky), nasopharyngeal carcinoma (southern China), PTLD (post-transplant), primary CNS lymphoma (HIV).
- CMV (HHV-5): Latent in mononuclear cells/macrophages. Congenital CMV = sensorineural hearing loss + periventricular calcifications + microcephaly. CMV retinitis in HIV (visual loss). Owl-eye (Cowdry A) intranuclear inclusions. Treatment: ganciclovir (UL97 kinase activates; resistance → foscarnet). Monospot-negative mono-like syndrome.
- HHV-6 (Roseola / Exanthem Subitum): High fever × 3 days → fever breaks → maculopapular rash trunk-to-extremities. Febrile seizures. Saliva transmission.
- HHV-8 (Kaposi Sarcoma): Vascular tumor (endothelial cell proliferation). Violaceous skin plaques. Immunocompromised — HIV or transplant. GI and pulmonary lesions also occur. Diagnose: PCR.
Herpes Virus Latency Sites
| Virus | Latency Site | Classic Exam Disease | Treatment |
|---|---|---|---|
| HHV-1 (HSV-1) | Trigeminal ganglion | Oral cold sores; temporal lobe encephalitis | Acyclovir IV (encephalitis) |
| HHV-2 (HSV-2) | Sacral ganglion | Genital herpes; neonatal herpes; meningitis | Acyclovir/valacyclovir |
| HHV-3 (VZV) | Dorsal root / trigeminal ganglion | Chickenpox; shingles; PHN | Acyclovir/valacyclovir |
| HHV-4 (EBV) | B cells (CD21 receptor) | Mono; Burkitt's; nasopharyngeal CA; PTLD | Supportive (no antivirals for mono) |
| HHV-5 (CMV) | Mononuclear cells / macrophages | Congenital; retinitis; colitis; esophagitis | Ganciclovir (resistance → foscarnet) |
| HHV-6 | — | Roseola (exanthem subitum) | Supportive |
| HHV-8 (KSHV) | — | Kaposi sarcoma | ART; chemotherapy for advanced |
EBV Malignancy Map
Burkitt's lymphoma: t(8;14). African child = jaw mass; European/adult = abdominal mass. Starry sky pattern on biopsy. Rapidly growing.
Nasopharyngeal carcinoma: Southern China ancestry + nosebleed + nasal polyps → EBV association.
PTLD: Transplant patient, immunosuppression ↑ → B-cell proliferation all over body.
Primary CNS lymphoma: HIV + ring-enhancing lesion (mimics toxoplasmosis — differentiate by empiric toxo treatment: if no response, biopsy for CNS lymphoma).
PHN Treatment — Avoid TCAs in Elderly
Post-herpetic neuralgia: gabapentin or pregabalin (first-line if elderly, BPH, or high fall risk). TCAs (amitriptyline, nortriptyline) = anti-H1 (sedation) + anti-α1 (orthostatic hypotension + fall risk) + anti-muscarinic (urinary retention, delirium). In elderly or BPH → pick gabapentin/pregabalin on the exam.
Monospot Test — Key Traps
Monospot (heterophile antibody test) detects antibodies against sheep/horse RBC antigens. Positive in EBV mono. False-negative in very early infection, infants. CMV causes monospot-NEGATIVE mono-like syndrome. On the exam: if monospot negative + mono picture → think CMV.
EP502
Toxoplasmosis & Candida Vulvovaginitis - HIV Prophylaxis Thresholds
- Toxoplasmosis: CD4 <100 → ring-enhancing lesion in brain of HIV patient. Prophylaxis: TMP-SMX (same as PCP). Treatment: pyrimethamine + sulfadiazine (NOT TMP-SMX for treatment).
- Candida vulvovaginitis: pH ≤4.5, pseudohyphae on wet prep, thick white discharge. Diabetic or recent antibiotic use. Treatment: oral fluconazole (single dose). Visual: branching Y-shaped pseudohyphae.
- Nocardia (RR bonus): Immunocompromised (transplant, diabetes). Lung + brain + skin abscesses. Acid-fast POSITIVE filamentous branching rods (not TB!). Treatment: TMP-SMX ×6 months.
- Cryptosporidium parvum: HIV with watery diarrhea (CD4 very low, often <50). Acid-fast positive oocysts. Treatment: nitazoxanide or paromomycin.
- EBV lymph node pathology: Viral infection → paracortex hyperplasia (T-cell zone). Bacterial → germinal center hyperplasia (B-cell zone). Absent paracortex = T-cell deficiency (DiGeorge, SCID). Absent germinal centers = B-cell deficiency (Bruton's agammaglobulinemia, Hyper-IgM syndrome).
Toxo vs CNS Lymphoma — Exam Differentiation
| Feature | Toxoplasmosis | Primary CNS Lymphoma |
|---|---|---|
| CD4 | Usually <100 | Usually <50 |
| Imaging | Ring-enhancing, often multiple | Ring-enhancing, often periventricular/single |
| Serology | Toxo IgG positive | EBV PCR positive in CSF |
| Approach | Empiric pyrimethamine + sulfadiazine × 2 weeks | Biopsy if no response to toxo treatment |
Acid-Fast Organisms That Are NOT TB
Nocardia asteroides — acid-fast, filamentous, branching rods. Lung + brain + skin in immunocompromised. Treat: TMP-SMX.
Cryptosporidium — acid-fast oocysts. Watery diarrhea in HIV. Treat: nitazoxanide.
Mycobacterium marinum — skin/soft tissue. Aquarium/fish tank exposure. Treat: clarithromycin ± rifampin.
MAC — disseminated in advanced HIV. Treat: clarithromycin + ethambutol ± rifabutin.
Systemic Bacterial Infections — Septic Joint & Osteomyelitis
Septic arthritis and osteomyelitis are Staph aureus stories with specific exceptions for age, host, and exposure — and each has its own mechanism of spread, diagnostic sequence, and treatment duration. Know both inside out: the USMLE tests mechanism of spread, gram stain-guided antibiotic selection, and imaging order with equal frequency.
EP492
The Clutch Septic Joint Podcast
- First step: Red, hot, tender monoarticular joint → arthrocentesis immediately. Most common joint = knee. Most common mechanism = hematogenous spread (synovium has no basement membrane).
- Most common causes: Non-gonococcal: #1 Staph aureus, #2 Strep pneumoniae. Gonococcal: young sexually active patient, polyarthralgias, tenosynovitis, pustular skin lesions, small joints (fingers/toes). Culture of synovial fluid often negative in GC — culture urethra/cervix instead.
- Prosthetic joint: <3 months after implant = direct inoculation (Staph epidermidis / biofilm). >3 months = hematogenous. Infected hardware MUST be removed.
- WBC count trap: Septic arthritis ≠ always >50,000 WBC. GC arthritis, fungal, mycobacterial, prosthetic joint infections can all have <50,000. Do not use this cutoff to exclude septic arthritis.
- IV drug users: Sternoclavicular joint involvement → IV drug use (track marks). Get blood cultures in addition to arthrocentesis.
Gram Stain-Guided Antibiotic Selection — Septic Arthritis
| Gram Stain Result | Likely Bug | Antibiotic |
|---|---|---|
| No organisms seen (empiric) | Unknown | Vancomycin + 3rd-gen cephalosporin (ceftriaxone or ceftazidime) |
| Gram-positive cocci | Staph aureus (worry MRSA) | Vancomycin |
| Gram-negative cocci | Neisseria gonorrhoeae | Ceftriaxone ± doxycycline or azithromycin (cover Chlamydia) |
| Gram-negative rods (no Pseudomonas concern) | Enteric GNR | 3rd-gen cephalosporin (ceftriaxone) |
| Gram-negative rods (Pseudomonas risk: IV drug use, puncture wound) | Pseudomonas | Ceftazidime (anti-pseudomonal 3rd-gen) + gentamicin |
Management Algorithm — Septic Joint
1. Arthrocentesis (gram stain + culture + cell count)
2. Blood cultures
3. Imaging (X-ray → MRI if needed)
4. Surgical drainage (needle aspiration preferred; OR if cannot aspirate)
5. IV antibiotics (4–6 weeks)
6. Remove hardware if prosthetic joint infected
Gonococcal Arthritis — Key Exam Points
Young sexually active patient. Classic triad: migratory polyarthralgias → tenosynovitis → pustular/vesicular skin lesions. Then settles into one joint (oligoarthritis). Culture synovial fluid often negative — culture urethra, cervix, pharynx, rectum. Always screen for other STIs (HIV, syphilis, chlamydia). Ceftriaxone is treatment — check for co-infection with Chlamydia (add doxycycline or azithromycin).
EP524
The Clutch Osteomyelitis Podcast
- Hallmark presentation: Bone pain + fever. Most common cause overall = Staph aureus. Most common cause in sickle cell disease = Salmonella (#1); Staph aureus (#2). Sickle cell osteomyelitis: Salmonella is the answer unless it's not a choice.
- Classic scenarios: IV drug user + vertebral pain → hematogenous vertebral osteomyelitis (Staph aureus). Immigrant from TB-endemic area + vertebral → Pott's disease (TB). Diabetic foot ulcer + probe-to-bone test positive → contiguous-spread osteomyelitis (polymicrobial). Nail puncture wound through shoe → Pseudomonas osteomyelitis. Thoracic surgery → sternal osteomyelitis.
- Workup sequence: Step 1 = imaging (X-ray first, then MRI — MRI is gold standard for osteomyelitis). Step 2 = blood cultures (positive in ~50% of hematogenous cases). Step 3 = bone biopsy/culture (definitive/confirmatory test).
- Treatment: IV vancomycin + gram-negative coverage (ceftriaxone for non-Pseudomonas; ceftazidime or cefepime for Pseudomonas). Duration: 4–6 weeks. Pott's disease: RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) + vitamin B6 (isoniazid → B6 deficiency).
- Surgery indications: Neurodeficits + vertebral osteomyelitis, unstable spine, or failure of antibiotic therapy. Also remove infected orthopedic hardware.
Osteomyelitis by Mechanism & Bug
| Scenario | Mechanism | Likely Bug(s) | Antibiotic |
|---|---|---|---|
| General (hematogenous) | Hematogenous | Staph aureus | Vancomycin + ceftriaxone |
| Sickle cell disease | Hematogenous | Salmonella (#1), Staph aureus (#2) | Fluoroquinolone or ceftriaxone |
| IV drug user (vertebral) | Hematogenous | Staph aureus | Vancomycin |
| TB-endemic immigrant (spine) | Hematogenous | M. tuberculosis (Pott's disease) | RIPE × 6–9 months + B6 |
| Diabetic foot ulcer (exposed bone) | Contiguous spread | Polymicrobial | Broad-spectrum |
| Nail puncture wound | Direct inoculation | Pseudomonas aeruginosa | Ceftazidime or cefepime + gentamicin |
| Post-surgical / trauma | Direct inoculation | Polymicrobial | Broad-spectrum |
Imaging Sequence on the Exam
X-ray first — may show lytic lesions, periosteal elevation, or cortical erosion (early infection often looks normal). MRI if X-ray is negative or equivocal — most sensitive/specific for osteomyelitis. CT only if MRI unavailable. Bone biopsy = confirmatory test (culture guides antibiotic de-escalation). Do NOT skip to bone biopsy without imaging first.
Vector-borne & Tropical Diseases — Travel Medicine
Travel medicine questions reward knowing geography, vector, unique clinical feature, and one treatment drug. The USMLE increasingly gives non-specific vignettes that require you to synthesize the travel history with a constellation of findings — the "two-key" method: geography + signature finding. Vaccine knowledge (live vs inactivated, contraindications) appears in every exam cycle.
EP631
Travel Medicine Part A — Malaria Prophylaxis & Geographic Vaccines
- Pre-travel vaccines: Give 2–4 weeks before travel (time to mount antibody response). Live attenuated vaccines (yellow fever, oral typhoid, MMR, varicella) = contraindicated in immunocompromised (CD4 <200), pregnancy, age <6–12 months.
- Malaria prophylaxis drugs: Atovaquone-proguanil (inhibits ETC + folate; contraindicated in renal failure). Mefloquine (contraindicated in seizure disorder, psychiatric illness, cardiac conduction abnormalities). Doxycycline (photosensitivity — "SAT for photo": Sulfonamide, Amiodarone, Tetracyclines; avoid in pregnancy on USMLE).
- Malaria basics: Plasmodium species carried by Anopheles mosquito. Prevention: pesticide-treated mosquito nets. Prophylaxis: start before travel, continue after return. Chloroquine-resistant areas → atovaquone-proguanil or mefloquine or doxycycline.
- Yellow fever vaccine: Live attenuated. Carried by Aedes mosquito. Required for entry to sub-Saharan Africa (e.g., Nigeria). Flavivirus. Presents with high fever + jaundice + bradycardia (pulse-temperature dissociation) + AKI (proteinuria). Hepatocyte necrosis → hemorrhage. Lifelong immunity after 1 dose. Contraindicated: age <6 months, pregnancy, immunocompromised, egg allergy, age >60 (relative), absent thymus (DiGeorge/SCID).
- Typhoid vaccine: Two forms — oral (live attenuated, 4 doses) vs injectable (polysaccharide, inactivated, 1 dose). Immunocompromised → injectable only, not oral.
Malaria Prophylaxis — Drug Selection Table
| Drug | Mechanism | Contraindications | Notes |
|---|---|---|---|
| Atovaquone-proguanil | Inhibit mitochondrial ETC + folate synthesis | Renal failure (CrCl <30) | Least resistance; most expensive |
| Mefloquine | Disrupts heme detox (unclear) | Seizure disorder; psychiatric illness; AV block | Weekly dosing; vivid dreams common |
| Doxycycline | 30S ribosomal inhibitor (protein synthesis) | Pregnancy (USMLE avoids); children under 8 (use with caution) | Photosensitivity; start 1–2 days before; continue 4 weeks after |
| Chloroquine | Inhibits heme polymerization | Chloroquine-resistant Plasmodium regions | Safe in pregnancy; use only if P. vivax/ovale without resistance |
Mefloquine Contraindication Mnemonic
Think "the crazy heart" — mefloquine is contraindicated in psychiatric illness (psychosis, depression, anxiety), seizure disorders, and cardiac conduction abnormalities (AV nodal disease). Similar to interferon-alpha (contraindicated in MDD/suicidal ideation).
Photosensitivity Drug Mnemonic — SAT for Photo
S = Sulfonamides | A = Amiodarone | T = Tetracyclines
Patient takes doxycycline for malaria prophylaxis, goes to the beach, gets a skin rash that worsens in the sun → photosensitivity from tetracycline class.
EP632
Travel Medicine Part B — Typhoid, Hep A, Dengue, Leptospirosis, Schistosomiasis
- Typhoid fever (Salmonella typhi): Fecal-oral. Stepladder fever progression + relative bradycardia (pulse-temperature dissociation) + rose spots (salmon-colored macules, lower abdomen) + constipation early → bloody diarrhea later. Diagnosis: blood culture (days 1–7); stool/urine culture or bone marrow culture (days >7). Treatment: fluoroquinolone or azithromycin or ceftriaxone. Complication: intestinal perforation → exploratory laparotomy.
- Hepatitis A: Picornavirus. Fecal-oral. Incubation ~1 month. Fever + jaundice + elevated LFTs. Severity increases with age (children often asymptomatic). No chronic infection. Anti-HAV IgM = acute; IgG = past/immune. Pre-existing liver disease → risk of fulminant hepatitis. Prevention: inactivated vaccine × 2 doses (0 and 6–12 months). Post-exposure prophylaxis = vaccine or Ig within 2 weeks.
- Dengue fever: Aedes mosquito. Thrombocytopenia + severe myalgias ("breakbone fever") + rash. Dengue hemorrhagic fever: capillary leak + bleeding diathesis. Returning traveler + thrombocytopenia = dengue until proven otherwise. No specific treatment (supportive).
- Schistosomiasis: Freshwater exposure. Eggs in bladder (S. haematobium → hematuria → bladder cancer) or intestines/liver (cirrhosis). Egypt, sub-Saharan Africa, Middle East. Eosinophilia (parasitic). Treatment: praziquantel.
- Ebola (hemorrhagic fever): Sub-Saharan Africa. Severe DIC, multi-organ failure. Transmission: infected body fluids — including cremated remains. Mortician handling body of Ebola patient = USMLE vignette.
Returning Traveler Differential — By Symptom
| Finding | Top Dx | Key Clue |
|---|---|---|
| Thrombocytopenia | Dengue #1; Rocky Mountain spotted fever (if US travel) | Dengue = Aedes; RMSF = Dermacentor tick |
| Jaundice | Hep A; Yellow fever; Leptospirosis; Malaria | Malaria = indirect hyperbilirubinemia (hemolysis) |
| Hemorrhage/bleeding | Yellow fever; Dengue; Ebola/Lassa fever | Ebola = DIC + multi-organ failure + Africa |
| Hematuria (traveler) | Schistosomiasis | Africa; freshwater; eosinophilia |
| Fever + relative bradycardia | Typhoid (Salmonella typhi); Leptospirosis | Typhoid = rose spots; Lepto = conjunctival suffusion |
| Chest X-ray interstitial infiltrate post-earthquake | Coccidioidomycosis | Valley fever — SW US; erythema nodosum |
| Heart failure + South America travel | Chagas disease (Trypanosoma cruzi) | Dilated cardiomyopathy; achalasia |
Typhoid Complications You Must Know
Intestinal perforation: 2–3 weeks into illness. Signs of peritonitis + guarding → exploratory laparotomy. Do NOT think this is only a trauma question.
Pulse-temperature dissociation: Temperature ↑ but pulse NOT rising proportionally. Classic for typhoid and leptospirosis. Analogous to albuminocytologic dissociation in GBS — two things that should go together, don't.
Geography Quick Map
| Region | Think |
|---|---|
| Sub-Saharan Africa / Amazon basin | Yellow fever (Aedes), malaria, Ebola, schistosomiasis |
| South America (heart failure, achalasia) | Chagas (T. cruzi) |
| New England / Northeast US | Lyme (Borrelia), babesiosis (Maltese cross, Ixodes), anaplasmosis |
| Midwest US (Wisconsin, Milwaukee) | Ehrlichiosis (lone star tick, monocyte morulae) |
| SW US / earthquake sites | Coccidioidomycosis (valley fever) |
| Post-hurricane / flood / tropical | Leptospirosis (conjunctival suffusion, liver + kidney failure) |
| Egypt / Middle East | Schistosomiasis |
RR 101EP480
Rapid Review — Leptospirosis, Tick-Borne Diseases, Ehrlichiosis vs Anaplasmosis
- Ehrlichiosis vs Anaplasmosis: Both: morulae (mulberry-like inclusions in cytoplasm); both treated with doxycycline. Ehrlichia = monocytes (kidney-bean nucleus = mononuclear cell). Anaplasma = neutrophils (polymorphonuclear = multi-segmented nucleus). Ehrlichia = lone star tick; Anaplasma = Ixodes tick. Ehrlichia may have rash; Anaplasmosis = NO rash.
- Babesiosis: Ixodes tick. Infects red blood cells (not WBCs). Hemolysis → indirect hyperbilirubinemia + anemia + jaundice. Blood smear: Maltese cross pattern. New England. Treatment: atovaquone + azithromycin.
- Leptospirosis: Rodent urine exposure (plumbers, lifeguards, post-hurricane). Conjunctival suffusion (eyes bright red). Liver + kidney = two organs targeted. Weil's disease = leptospirosis with liver + renal failure. Treatment: penicillin. Jarisch-Herxheimer reaction may occur after starting antibiotics (spirochete).
- Leptospirosis as spirochete: USMLE may put "spirochete" as the answer instead of "Leptospira interrogans." Other spirochetes: Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme). All treated with penicillin or doxycycline.
Tick-Borne Disease Comparison
| Disease | Bug | Tick Vector | Target Cell | Blood Smear | Rash | Treatment |
|---|---|---|---|---|---|---|
| Ehrlichiosis | Ehrlichia chaffeensis | Lone star tick | Monocytes (kidney-bean nucleus) | Morulae in monocytes | May have rash | Doxycycline |
| Anaplasmosis | Anaplasma phagocytophilum | Ixodes tick | Neutrophils (multi-segmented nucleus) | Morulae in neutrophils | NO rash | Doxycycline |
| Babesiosis | Babesia microti | Ixodes tick | Red blood cells | Maltese cross (tetrad) | None | Atovaquone + azithromycin |
| Lyme disease | Borrelia burgdorferi | Ixodes tick | — | — | Erythema migrans (bull's-eye) | Doxycycline |
| RMSF | Rickettsia rickettsii | Dermacentor tick | Endothelium | — | Petechiae: wrists/ankles → trunk | Doxycycline (even in kids, pregnancy) |
RMSF — Treat With Doxycycline Even in Pregnancy
Rocky Mountain spotted fever: if untreated the patient will die. Doxycycline is the treatment regardless of pregnancy or age. This is one of the few scenarios where the risk-benefit of doxycycline outweighs concerns. Thrombocytopenia + petechial rash spreading from wrists to trunk = RMSF until proven otherwise.
EP483
Parvovirus B19 Polyarthritis & Leptospirosis
- Parvovirus B19: Kindergarten teacher / daycare worker with symmetric acute polyarthritis (MCP joints, feet, hands). Single-stranded DNA virus infects red blood cell precursors → aplastic crisis (sickle cell AND thalassemia). Hydrops fetalis if mom infected. NOT a rheumatoid arthritis diagnosis (RA needs ≥6 weeks of symptoms to diagnose).
- Leptospirosis detail: Conjunctival suffusion = buzzword. Post-hurricane, post-flood environments. Liver AND kidney failure = Weil's disease. Treatment: penicillin. Jarisch-Herxheimer occurs when treating spirochetes (fever, flushing, rigors — from massive cytokine release).
- Schistosomiasis (EP483 detail): African/Egyptian immigrant + hematuria (S. haematobium → bladder). Also liver cirrhosis (eggs in liver portal tracts). Increased risk squamous cell carcinoma of the bladder. Egypt = classic association. Treatment: praziquantel.
- Nocardia vs Actinomyces: Nocardia = acid-fast, aerobic, filamentous rods; immunocompromised; lung/brain/skin; TMP-SMX. Actinomyces = NOT acid-fast, anaerobic; draining sulfur granules from jaw (cervicofacial), lung, or abdomen; treatment penicillin.
Parvovirus B19 — Three Exam Presentations
| Population | Presentation | Why |
|---|---|---|
| Children (slapped-cheek) | Erythema infectiosum: bright red facial rash + lacy reticular rash extremities | Immune complex deposition |
| Hemoglobinopathy (SCD, thalassemia) | Aplastic crisis — sudden hemoglobin drop, reticulocytopenia | Infects RBC precursors → stops production |
| Adults / daycare workers | Symmetric acute polyarthritis (hands, feet, wrists) | Immune complex arthritis (not RA — no 6-week criterion) |
| Fetus (infected mother) | Hydrops fetalis — fetal heart failure, edema | Fetal RBC precursors destroyed → severe anemia |
Antimicrobial Stewardship & Resistance — MRSA, VRE, MDR Organisms
Antibiotic selection on the USMLE is not pharmacology — it's clinical decision-making. The exam tests which antibiotic to use for which clinical scenario, NOT mechanisms of action (with a few exceptions). Learn the drug-to-indication map, then layer in the coverage tables for MRSA, Pseudomonas, and ESBL organisms.
EP554
What Is This Antibiotic Used For? (Extremely HY for Step 1–3)
- Penicillin: Syphilis (#1 use). Streptococcal pharyngitis. Actinomyces (draining sulfur granules). Rheumatic fever prophylaxis. Leptospirosis.
- Amoxicillin: Acute otitis media (first-line); Listeria meningitis (add to ceftriaxone + vancomycin if age >50 or neonate); chorioamnionitis (ampicillin + gentamicin); Lyme disease prophylaxis in pregnancy. Augmentin (amox + clavulanate) = second-line otitis media.
- Ceftriaxone (3rd-gen): Gonorrhea treatment; Neisseria meningitis; CAP (inpatient); SBP (spontaneous bacterial peritonitis); GI infections with metronidazole; close-contact prophylaxis for meningococcal (alternate: rifampin). Ceftazidime = only 3rd-gen covering Pseudomonas. Cefepime (4th-gen) = febrile neutropenia + Pseudomonas coverage.
- Vancomycin: MRSA infections (IV). C. diff colitis (oral vancomycin). Empiric coverage for gram-positive cocci in septic joint, osteomyelitis, meningitis.
- Linezolid: VRE and MRSA. 50S inhibitor. MAOI activity → tyramine hypertensive crisis (cheese) + serotonin syndrome if combined with SSRIs. Also: neutropenia with prolonged use.
- TMP-SMX (Bactrim): PCP treatment and prophylaxis. Toxoplasmosis prophylaxis. MRSA skin/soft tissue infections. UTIs. Nocardia. Side effects: neutropenia, G6PD hemolysis.
Coverage by Organism — Exam Master Table
| Target | Drug(s) of Choice | Notes |
|---|---|---|
| MSSA | Nafcillin / dicloxacillin / oxacillin / cephalexin | Mastitis = dicloxacillin/oxacillin. 1st-gen ceph works. |
| MRSA (skin/soft tissue) | TMP-SMX or doxycycline | Oral for outpatient MRSA skin infection |
| MRSA (invasive/systemic) | Vancomycin (first-line); linezolid; daptomycin | Vancomycin is the go-to for IV MRSA |
| VRE | Linezolid or daptomycin | Linezolid: MAOI → serotonin syndrome with SSRIs |
| Pseudomonas | Ceftazidime (3rd-gen); cefepime (4th-gen); aminoglycosides; fluoroquinolones; carbapenems | Never pick piperacillin-tazobactam on USMLE |
| ESBL organisms | Carbapenems (imipenem, meropenem) | Carbapenem = ICU-level severity |
| C. diff | Oral vancomycin or fidaxomicin (first-line); NOT metronidazole (old approach) | Metronidazole = outdated for C. diff treatment on current exams |
| Anaerobes | Metronidazole or clindamycin; carbapenems | Clindamycin = toxin-mediated infections (necrotizing fasciitis, toxic shock) |
Antibiotic Quick Reference — Indications
| Antibiotic | Key USMLE Indications | Watch For |
|---|---|---|
| Penicillin G | Syphilis; group A strep; actinomyces; rheumatic fever | Jarisch-Herxheimer when treating syphilis/leptospirosis |
| Amoxicillin | AOM (1st-line); Listeria; Lyme (pregnant); chorioamnionitis (with gent) | Amoxicillin + mono → full-body rash (NOT allergy) |
| Ampicillin-sulbactam | Epiglottitis; mastoiditis | Not the same as pip-tazo (which is never correct on USMLE) |
| Cefazolin (1st-gen) | Surgical prophylaxis (ANSEF) | Before every surgery |
| Ceftriaxone (3rd-gen) | Gonorrhea; meningitis; CAP; SBP; typhoid | Pediatric: use cefotaxime (ceftriaxone → biliary cholestasis in neonates) |
| Macrolides (azithro/clarithro) | CAP; Legionella; pertussis; walking pneumonia (atypicals); H. pylori (triple: macrolide + amox + PPI) | Azithro for COPD exacerbation; clarithro preferred for H. pylori |
| Clindamycin | Necrotizing fasciitis; anaerobes; endometritis (+ gentamicin); MRSA (covers) | C. diff association; inhibits 50S → anti-toxin effect |
| Metronidazole | C. diff (old); Trichomonas; Giardia; E. histolytica; BV; anaerobes; H. pylori (quadruple: metro + bismuth + tetracycline + PPI) | Disulfiram reaction with alcohol |
| Doxycycline | RMSF; chlamydia; Lyme; malaria prophylaxis; acne; PID | Photosensitivity; avoid in pregnancy (USMLE); tetracyclines |
| Rifampin | TB (RIPE); close contact meningococcal prophylaxis; H. flu type B prophylaxis; prosthetic valve endocarditis adjunct; M. marinum | CYP450 inducer (reduces contraceptive efficacy) |
| Nitrofurantoin | Cystitis in women (including pregnant); ONLY for cystitis — not pyelonephritis, not men | Never use in men on USMLE |
| Fosfomycin | UTIs (especially multidrug-resistant) | Single dose option |
| Daptomycin | MRSA; VRE | Inactivated by pulmonary surfactant → do NOT use for pneumonia |
| Carbapenems | ESBL organisms; ICU-level gram-negative infections; anaerobes | If patient is on a carbapenem, they are critically ill |
Linezolid Drug Interactions — High-Yield for Boards
Linezolid = MAOI (monoamine oxidase inhibitor)
1. Tyramine-rich foods (cheese, wine, cured meats) → hypertensive crisis
2. Combined with SSRI/SNRI → serotonin syndrome (clonus, hyperreflexia, hyperthermia, agitation)
Classic vignette: patient on SSRI for depression develops endocarditis → started on linezolid for VRE/MRSA → develops serotonin syndrome.
H. pylori Regimens — Get These Straight
Triple therapy: Macrolide (clarithromycin) + amoxicillin + PPI
Quadruple therapy: Metronidazole + bismuth subsalicylate + tetracycline + PPI
(Common exam error: people say macrolide in quadruple — it's metronidazole, not a macrolide)
Pseudomonas Coverage — Summary
Pseudomonas is covered by: fluoroquinolones, aminoglycosides, ceftazidime (3rd-gen ceph), cefepime (4th-gen ceph), carbapenems. Piperacillin-tazobactam also covers it but is NEVER the right answer on USMLE.
EP547
Antimicrobial Resistance - Beta-Lactamases, MRSA, VRE & ESBL
- Furosemide sulfa allergy trap: Furosemide is a sulfonamide-based loop diuretic. Patient with documented sulfa anaphylaxis needing diuresis → use ethacrynic acid (only non-sulfa loop diuretic). Ethacrynic acid = most ototoxic loop diuretic.
- Ototoxic drugs to know: Ethacrynic acid (#1 ototoxic loop diuretic), aminoglycosides (gentamicin, amikacin, tobramycin), vancomycin, cisplatin (platinum-based chemo).
- C. diff management update: Oral vancomycin or fidaxomicin (first-line for ALL cases). Metronidazole is no longer recommended as first-line. Toxic megacolon (transverse colon >6 cm) from C. diff → NPO + surgery if bowel ischemia.
- Sulfonylurea vs meglitinide: Both close KATP channels on beta cells → insulin release. Meglitinides (repaglinide, nateglinide) = shorter acting, less hypoglycemia, safe in sulfa allergy. Use meglitinides if patient has sulfa allergy or needs meal-time only coverage.
Loop Diuretics — Side Effect Profile
| Drug | Sulfa-Based? | Ototoxicity | Key Use |
|---|---|---|---|
| Furosemide | Yes | Moderate | CHF, edema, hypercalcemia (calcium wasting) |
| Bumetanide | Yes | Moderate | CHF (loop diuretic alternative) |
| Torsemide | Yes | Low | CHF with better bioavailability |
| Ethacrynic acid | No (phenoxyacetic acid) | Highest of all | CHF in sulfa-allergic patients |
EP632
Parasite Lifecycles - Schistosomiasis & Cutaneous Larva Migrans
- Toxic megacolon mechanisms: C. diff most classic, but also: opioid ileus with superimposed infection, inflammatory bowel disease (UC/Crohn). Transverse colon >6 cm = toxic megacolon. Alternate exam name = "inflammatory colonic dilation." Management: NPO, bowel rest; surgery if ischemia develops.
- Chagas disease (Trypanosoma cruzi): South America. Reduviid (kissing) bug. Dilated cardiomyopathy + achalasia (megaesophagus) + megacolon. Exam: patient returns from Amazon basin with heart failure → Chagas until proven otherwise.
- Tinea/Dermatophyte order of frequency: Trichophyton (#1 most common for all tinea types), Microsporum (#2), Epidermophyton (#3). Tinea corporis and capitis = same bug order. Onychomycosis and tinea capitis → systemic therapy required (oral terbinafine > griseofulvin; griseofulvin = CYP450 inducer).
- USMLE alternate names (surrogate strategy): Tinea corporis = "ringworm," toxic megacolon = "inflammatory colonic dilation," Hirschsprung's = "congenital megacolon" or "colonic aganglionosis," Weil's disease = "leptospirosis with liver + kidney failure," yellow fever = "flavivirus," hep A = "picornavirus."
Protozoan Parasites — Exam Quick Reference
| Organism | Disease | Classic Clue | Treatment |
|---|---|---|---|
| Plasmodium falciparum | Malaria | Anopheles mosquito; Africa/Asia; hemolysis | Atovaquone-proguanil; artemether-lumefantrine |
| Toxoplasma gondii | Toxoplasmosis | HIV + ring-enhancing brain lesion; cat litter; undercooked meat | Pyrimethamine + sulfadiazine |
| Trypanosoma cruzi | Chagas disease | South America; dilated cardiomyopathy + achalasia; Romana's sign | Benznidazole or nifurtimox |
| Trypanosoma brucei | Sleeping sickness | Sub-Saharan Africa; tsetse fly; CNS → coma | Suramin (early); melarsoprol (late, CNS) |
| Leishmania donovani | Visceral leishmaniasis (kala-azar) | India/Africa; sandfly; hepatosplenomegaly | Liposomal amphotericin B |
| Entamoeba histolytica | Amebic colitis/liver abscess | Bloody diarrhea; right upper quadrant pain; "anchovy paste" abscess | Metronidazole |
| Giardia lamblia | Giardiasis | Camping/well water; foul-smelling watery diarrhea; trophozoites (pear-shaped with 2 nuclei) | Metronidazole |
| Cryptosporidium parvum | Cryptosporidiosis | HIV + watery diarrhea; acid-fast oocysts; swimming pools | Nitazoxanide; paromomycin (HIV) |
CYP450 Inducers — Griseofulvin Integration
Griseofulvin is a CYP450 inducer → reduces efficacy of oral contraceptive pills → unintended pregnancy on the exam. Classic vignette: woman on OCP for contraception starts griseofulvin for tinea capitis/onychomycosis → becomes pregnant. Other CYP450 inducers: Rifampin, Carbamazepine, Phenobarbital, Phenytoin, St. John's Wort, Griseofulvin (mnemonic: RCPPS-G or "Ring-worn Crazy Professors Prefer St. Gris").
Also Covered In Other Episodes
Divine’s rapid-review episodes mix several systems into one recording. These episodes are filed under another system but contain a substantial Infectious Disease segment. The title names the whole episode; the bullets are the Infectious Disease portion only.
RR 68 EP358EP358
Rapid Review 68 - CNS Toxoplasmosis, Esophageal Varices, Actinic Keratosis, Parvovirus B19
Cross-listed. This episode is filed under MSK & Rheumatology. Below is only its Infectious Disease content.
- CNS toxoplasmosis in an HIV patient presenting with ring-enhancing lesions, headache, fever and altered mental status
- Treatment vs prophylaxis of toxoplasmosis: pyrimethamine plus sulfadiazine to treat, TMP-SMX to prophylax, spiramycin in pregnancy
- Brain biopsy for primary CNS lymphoma when a presumed toxo patient does not improve
- Vulvovaginal candidiasis: risk groups (HIV, diabetes, recent antibiotics, smoking), pseudohyphae on wet prep, vaginal pH 4.5 or less, topical/oral azoles
- Parvovirus B19 as a cause of aplastic crisis, slapped-cheek rash and hydrops fetalis
RR 115 EP536EP536
Rapid Review 115 - Presbycusis & Ototoxic Drugs, Nicotine Withdrawal, Migraine, MAOI Crisis
Cross-listed. This episode is filed under MSK & Rheumatology. Below is only its Infectious Disease content.
- Infectious mononucleosis: fatigue and sore throat in a young patient, monospot test, EBV etiology
- Ampicillin rash in mono is not a true allergy and does not preclude future ampicillin or amoxicillin
- Acute HIV syndrome: fatigue, weight loss, fever, myalgias and generalized lymphadenopathy, with HIV testing and antiretroviral therapy
- Vancomycin uses referenced across vignettes (MRSA, C. diff, IV drug user endocarditis) and its ototoxicity
RR 63 EP335EP335
Rapid Review 63 - Tularemia, Toxic Shock Syndrome, Q Fever, Melioidosis, CMV
Cross-listed. This episode is filed under Gastrointestinal. Below is only its Infectious Disease content.
- Tularemia: rabbit exposure, painful ulcer with inguinal lymphadenopathy, 'ulceroglandular disease' as the derivative answer, Dermacentor tick vector
- Toxic shock syndrome from S. pyogenes (50% mortality) vs S. aureus (5%): tampons, nasal packing, IUD; source control, fluids, broad-spectrum antibiotics
- Q fever from Coxiella burnetii presenting as culture-negative endocarditis after animal-shelter exposure; serum antibody diagnosis
- Melioidosis from Burkholderia pseudomallei: diabetic patient with soil and water exposure, abscesses in brain and liver, blood cultures for diagnosis
- Rocky Mountain spotted fever from Rickettsia rickettsii: petechiae on wrists/ankles spreading inward, leukopenia, thrombocytopenia, hyponatremia, elevated LFTs
- CMV: heterophile-negative mononucleosis, owl's eye intranuclear inclusions, CMV retinitis in HIV, CMV colitis post-transplant
EP408
Rapid Review 81 - Postoperative Fever, Malignant Hyperthermia, Ludwig Angina, Dumping Syndrome
Cross-listed. This episode is filed under Gastrointestinal. Below is only its Infectious Disease content.
- Bacterial conjunctivitis with thick purulent discharge that reaccumulates after wiping; most commonly Staphylococcus aureus
- Pseudomonas causes conjunctivitis specifically in contact lens wearers
- Other Pseudomonas niches: otitis externa (most common cause, treated with acetic acid or fluoroquinolone otic drops), pneumonia in cystic fibrosis patients over 20, osteomyelitis after nail puncture
- Neutropenic and diabetic patients are prone to serious Pseudomonas infections
- Ludwig angina as a deep neck space cellulitis following an ear infection
RR 72 EP380EP380
Rapid Review 72 - Herpetic Whitlow, Aminoglycoside Toxicity, TMP-SMX, G6PD Deficiency
Cross-listed. This episode is filed under Emergency Medicine. Below is only its Infectious Disease content.
- Herpetic whitlow treated with oral, not IV, acyclovir
- HSV involvement of the temporal lobes with hemorrhagic CSF containing hundreds to thousands of red blood cells
- Aminoglycosides versus vancomycin for a kidney infection based on gram-negative versus gram-positive coverage
- TMP-SMX prophylaxis thresholds: toxoplasmosis below CD4 100 and Pneumocystis jirovecii below CD4 200
- Primaquine-triggered hemolysis in G6PD-deficient patients from malaria-endemic populations
RR 62 EP334EP334
Rapid Review 62 - Tay-Sachs vs Niemann-Pick, Brucellosis, Leptospirosis, Lyme Co-infections
Cross-listed. This episode is filed under Gastrointestinal. Below is only its Infectious Disease content.
- Brucellosis (undulant fever) from unpasteurized goat milk, treated with doxycycline plus rifampin or doxycycline plus an aminoglycoside; prevented by pasteurization
- Leptospirosis in plumbers, sewage workers and Hawaii exposures, with transaminase elevation, rising creatinine and conjunctival injection; ELISA then microscopic agglutination test, treated with doxycycline or a macrolide, and pulmonary involvement carrying 50-70% mortality
- Lyme disease from Borrelia burgdorferi via the Ixodes tick, requiring over 36 hours of attachment; CN VII palsy and third-degree AV block
- Lyme treatment by age and pregnancy status (doxycycline over 8, amoxicillin or cefuroxime otherwise) with IV ceftriaxone for Lyme meningitis or myocarditis; DEET and permethrin for prevention
- Differentiating anaplasmosis (pancytopenia), babesiosis (hemolytic anemia, Maltese cross, azithromycin plus atovaquone) and ehrlichiosis (leukopenia from suppressed TNF)