USMLE Step 1 Microbiology: 8 High-Yield Practice Questions
Microbiology accounts for ~10% of Step 1. The highest-yield areas are gram-stain characteristics, unique virulence factors, and clinical presentations that narrow to a specific organism. These 8 questions cover the patterns that appear most often.
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Evidence-based · For exam prep, not medical advice
update Updated October 2026
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Built by surgery and anesthesiology residents·Written for USMLE Step 1
High-Yield Topics Covered
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Gram-positive cocci (Staph, Strep)
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Gram-negative rods and their unique features
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Obligate intracellular organisms
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Encapsulated bacteria and asplenic patients
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Atypical pneumonia organisms
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Fungal infections and endemic mycoses
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Viral hepatitis comparison
Question 1 of 8Score: 0 / 0
Q1Gram-Negative Bacteria
A 4-year-old unvaccinated child presents with high fever, irritability, and a purpuric rash that does not blanch on pressure. Blood cultures grow gram-negative diplococci. What is the most likely organism?
A splenectomized patient presents with rapidly progressive sepsis. Which organisms pose the greatest risk in asplenic patients?
Explanation: The spleen filters encapsulated bacteria via opsonin-dependent phagocytosis. Without a spleen, patients are at risk for OPSI (overwhelming post-splenectomy infection) — primarily S. pneumoniae, H. influenzae type b, and N. meningitidis. Mnemonic: 'SHiN' = S. pneumoniae, H. influenzae, N. meningitidis. Vaccinate prior to elective splenectomy.
Q3Fungal Infections
A 25-year-old returns from the Ohio River Valley with fever, night sweats, and bilateral hilar lymphadenopathy on CXR. Skin test is negative. Bronchoscopy shows macrophages with intracellular yeast. Most likely organism?
Explanation: Histoplasma capsulatum: endemic to Ohio and Mississippi River valleys. Intracellular yeast within macrophages is pathognomonic. Presents like TB (bilateral hilar lymphadenopathy, granulomas). Skin test negative in disseminated or severe disease. Diagnose with urine antigen. Treat with itraconazole (mild) or amphotericin B (severe/disseminated).
Q4STI Pathogens
A sexually active 22-year-old woman has cervical discharge. Gram stain shows gram-negative intracellular diplococci within PMNs. She is allergic to penicillin. Most appropriate treatment?
Explanation: Neisseria gonorrhoeae: gram-negative intracellular diplococci in PMNs. Treatment: ceftriaxone (first-line regardless of penicillin allergy — cross-reactivity is low) + azithromycin or doxycycline for Chlamydia co-infection (treat empirically). Fluoroquinolone resistance is now widespread — no longer recommended. Ceftriaxone allergy is the only indication to consider alternatives.
Q5Anaerobes and GI Pathogens
A patient develops diarrhea 5 days after starting clindamycin for a skin infection. Stool studies show a toxin-producing organism. What is the most likely pathogen and mechanism?
Explanation: C. difficile colitis follows antibiotic disruption of normal flora (classically clindamycin, fluoroquinolones, cephalosporins, amoxicillin). Produces toxin A (mucosal damage) and toxin B (cytoskeletal disruption). Diagnose: PCR or toxin ELISA. Treat mild: oral vancomycin or fidaxomicin; severe: vancomycin ± metronidazole; recurrent: bezlotoxumab, fecal microbiota transplant.
Q6Viral Pathogens
A college student has fever, malaise, pharyngitis, lymphadenopathy, and splenomegaly. Monospot test is positive. What is the risk of administering amoxicillin?
Explanation: Infectious mononucleosis (EBV): administration of amoxicillin (or ampicillin) causes a diffuse maculopapular rash in nearly all patients — a classic boards trap. This is NOT a true penicillin allergy — it is EBV-specific and does not predict reaction to penicillin in the absence of mono. Other EBV complications: splenic rupture (avoid contact sports), Burkitt lymphoma, nasopharyngeal carcinoma.
Q7Opportunistic Infections
A 35-year-old HIV-positive patient (CD4 50) develops headache and fever. CSF shows India ink staining of a round, encapsulated organism. Most likely pathogen?
Explanation: Cryptococcus neoformans: encapsulated yeast, India ink (+) in CSF, urease (+), pigeon droppings exposure. Causes meningitis in CD4 <100. Diagnose: CSF India ink + cryptococcal antigen (most sensitive). Treat: amphotericin B + flucytosine (induction) → fluconazole (consolidation/maintenance).
Q8Atypical Organisms
Which organism is an obligate intracellular parasite that causes atypical pneumonia and can be diagnosed by Giemsa stain of sputum showing intracytoplasmic inclusions?
Explanation: Chlamydophila psittaci (psittacosis): obligate intracellular, bird exposure (parrots, pigeons), causes atypical pneumonia. Chlamydia species have both elementary bodies (infectious) and reticulate bodies (replicative). Intracytoplasmic inclusions seen on Giemsa/DFA staining. Treat: doxycycline. Chlamydophila pneumoniae causes walking pneumonia; Mycoplasma has no cell wall (cold agglutinins); Legionella grows on charcoal yeast extract.
What are the obligate intracellular organisms tested on Step 1?
Obligate intracellular organisms: Chlamydia, Rickettsia, Coxiella burnetii, Bartonella (facultative), and all viruses. Mnemonic: 'Chocolate Requires Cold Beer' — Chlamydia, Rickettsia, Coxiella, Bartonella. These cannot be cultured on standard media; diagnose by serology, PCR, or specialized culture.
What is the difference between bacteriostatic and bactericidal antibiotics?
Bacteriostatic drugs inhibit bacterial growth without killing (tetracyclines, macrolides, clindamycin, linezolid, sulfonamides, chloramphenicol — mnemonic: 'MCLSCT'). Bactericidal drugs kill bacteria (beta-lactams, aminoglycosides, fluoroquinolones, metronidazole, vancomycin). Clinical significance: for endocarditis, meningitis, and immunocompromised patients, bactericidal agents are preferred because host defenses cannot finish off inhibited organisms.
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