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.
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.
RR 109EP502
Rapid Review — Toxoplasmosis, Candida, Opportunistic Pearls
- 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.
RR 102EP483
Rapid Review — 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.
RR 125EP612
Rapid Review — Resistant Organisms & Antimicrobial Stewardship
- 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 |
RR 134EP638
Rapid Review — Pathogenic Mechanisms, Immune Evasion & Parasite Lifecycles
- 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").