Infectious Disease USMLE Practice Questions
Microbiology, antimicrobials, and clinical infections.
5 free infectious disease practice questions
Pick an answer and check it. After each question you get the same explanation StepGenie students see: the stem decoded clue by clue, the reasoning chain with its infographic, why every wrong option is wrong, and the trap the question was built around. Step 1 questions test mechanism; Step 2 CK questions ask for the next step.
A 32-year-old man presents with a 6-day history of low-grade fever, dry cough, and progressive shortness of breath that began while he was on vacation in Thailand. He was evaluated at an urgent care clinic there and started on cefuroxime without clinical improvement. His temperature is 38.2°C (100.8°F). On examination, breath sounds are decreased at both lung bases. Chest x-ray reveals diffuse patchy infiltrates. Sputum analysis shows numerous neutrophils but no organisms, and Giemsa stain demonstrates epithelial cells with cytoplasmic inclusion bodies. Which of the following properties of the most likely causal pathogen best explains this patient’s lack of response to the initial treatment?
Correct answer · B
Lack of peptidoglycan in cell wall
Decoding the stem
Step-by-step reasoning
Step 1 of 6
Dry cough, low-grade fever, and diffuse patchy infiltrates indicate atypical pneumonia rather than classic lobar pneumonia.
Step 2 of 6
Sputum with many neutrophils but no organisms on standard stain suggests an intracellular pathogen or one poorly visualized by Gram stain.
Step 3 of 6
Giemsa stain showing epithelial cells containing cytoplasmic inclusion bodies is characteristic of Chlamydia pneumoniae infection.
Step 4 of 6
Chlamydia species are obligate intracellular bacteria that lack a normal peptidoglycan layer in their cell wall.
Step 5 of 6
β-lactam antibiotics (like cefuroxime) target peptidoglycan cross-linking; without peptidoglycan, these drugs have no effective target.
Step 6 of 6
Therefore, the key property explaining treatment failure is the pathogen’s lack of peptidoglycan in its cell wall.
Why not the others?
A. Antigenic variation of adhesive pili
This option implies Neisseria gonorrhoeae, which evades immunity via pilus variation, BUT this causes urethritis/PID, not atypical pneumonia with inclusion bodies.
C. Enclosure by polysaccharide capsule
This implies encapsulated bacteria (e.g., S. pneumoniae), which cause lobar pneumonia responsive to β-lactams, BUT this patient has atypical features and no response to cefuroxime.
D. Formation of biofilms
Biofilms are typical of chronic device-related or cystic fibrosis infections (e.g., Pseudomonas, Staph), BUT this is an acute travel-related atypical pneumonia with Chlamydia features, not device-related disease.
E. Production of β-lactamase enzymes
This suggests classic resistance by drug degradation (e.g., some H. influenzae, S. aureus), BUT the main reason β-lactams fail against Chlamydia is absence of peptidoglycan, not enzyme-mediated resistance.
F. Rapid alteration of drug binding sites
This describes target site modification (e.g., MRSA PBP changes, macrolide-resistant bacteria), BUT again the fundamental issue here is that Chlamydia lacks the peptidoglycan target altogether.
Exam trap
The vignette pushes you toward generic antibiotic resistance mechanisms (β-lactamase, altered binding sites). The key is to recognize Chlamydia and recall its structural absence of peptidoglycan, not classic resistance evolution.
The bottom line
Chlamydia pneumoniae causes atypical pneumonia and lacks peptidoglycan, making β-lactam antibiotics like cefuroxime ineffective.
A 43-year-old man with HIV presents with signs and symptoms suggestive of a fungal infection. He is not currently taking antiretroviral therapy, and his CD4+ T-lymphocyte count is 98 cells/µL. Which of the following Candida infections is most likely to occur in this patient but would be very rare in an immunocompetent individual?
Correct answer · D
Esophagitis
Decoding the stem
Step-by-step reasoning
Step 1 of 5
CD4 count of 98 cells/µL in untreated HIV indicates advanced immunosuppression (AIDS range).
Step 2 of 5
In advanced HIV, Candida shifts from causing superficial mucocutaneous disease to invasive mucosal disease, especially esophagitis.
Step 3 of 5
Candida esophagitis presents predominantly in immunocompromised patients and is rare in immunocompetent individuals.
Step 4 of 5
Other Candida infections (oral thrush, vaginitis, intertrigo, some endocarditis cases) can occur in immunocompetent hosts under common predisposing conditions.
Step 5 of 5
Therefore, among the options, esophagitis is the Candida infection most characteristic of severe immunosuppression and rare in healthy individuals.
Why not the others?
A. Oral thrush
This option implies oropharyngeal candidiasis, which commonly occurs in immunocompetent individuals after antibiotics, inhaled steroids, or poor oral hygiene, BUT the question asks for an infection that is very rare in immunocompetent hosts.
B. Vaginitis
This option implies vulvovaginal candidiasis, which is very common in healthy women (e.g., after antibiotics, pregnancy, diabetes), BUT the question specifically wants a Candida infection that is unusual in immunocompetent individuals.
C. Intertrigo
This option implies cutaneous Candida infection in skin folds, which frequently affects immunocompetent people (obesity, moisture, friction), BUT it is not characteristic of severe immunosuppression and is far from rare in healthy hosts.
E. Endocarditis
This option implies Candida endocarditis, which occurs in IV drug users and those with prosthetic valves, many of whom can be immunocompetent; it is rare overall, BUT its occurrence is tied more to intravascular devices/IVDU than to CD4 count–driven immunosuppression like in this patient.
Exam trap
Students may associate any Candida infection with HIV and pick oral thrush because it’s classic, but the stem emphasizes severe immunosuppression (CD4 <100) and asks what would be very rare in immunocompetent individuals—that key phrase points specifically to esophageal involvement rather than common mucocutaneous forms.
The bottom line
Candida esophagitis occurs in patients with advanced immunosuppression (CD4 <100) and is rare in immunocompetent individuals; other Candida infections commonly occur in healthy hosts.
A 50-year-old man presents to the emergency department with acute right-sided facial weakness that he first noticed upon awakening this morning. One month ago, he developed right-sided neck pain and headache that began after returning from a hunting trip to New Hampshire; the symptoms resolved over a week with ibuprofen. Medical history is significant for hypertension well controlled on medication. He has a 35–pack-year smoking history and drinks 2 beers daily. Vital signs are within normal limits. Physical examination reveals right-sided drooping of both the upper and lower face. He has difficulty smiling and is unable to close his right eye. The remainder of the neurologic and general examination is normal. Which of the following is the most appropriate next step in diagnosis?
Correct answer · D
Enzyme‑linked immunosorbent assay
Decoding the stem
Step-by-step reasoning
- 1
Complete upper and lower facial droop on the right indicates a peripheral CN VII palsy rather than a central (UMN) lesion like stroke.
- 2
Recent hunting trip in New Hampshire (endemic for Lyme disease) plus transient neck pain/headache suggests prior Borrelia burgdorferi infection.
- 3
Lyme disease commonly causes isolated facial nerve palsy (often unilateral) as a manifestation of early disseminated/neurologic Lyme.
- 4
Diagnosis of Lyme disease in this setting is made with serologic testing rather than imaging or CSF in an otherwise stable patient.
- 5
CDC-recommended algorithm: screen with ELISA (or IFA) for Lyme antibodies, and confirm positives with Western blot.
- 6
Therefore, the most appropriate next diagnostic step is enzyme‑linked immunosorbent assay for Lyme serology.
Why not the others?
A. Western blot
This option implies confirmatory testing for Lyme (immunoblot), which is used after a positive or equivocal ELISA, BUT the question asks for the next step in diagnosis, which is initial screening with ELISA.
B. Polymerase chain reaction of the facial skin
This option implies direct PCR detection from skin, which is used mainly from erythema migrans lesions or synovial fluid, BUT this patient has no rash or joint effusion and standard practice is serology, not skin PCR, for neurologic Lyme.
C. Cerebrospinal fluid analysis
This option implies Lyme meningitis or CNS infection, which would cause meningitic signs (fever, neck stiffness, AMS), BUT this patient has isolated facial palsy, normal exam, and no red flags warranting lumbar puncture.
E. Noncontrast CT
This option implies concern for acute stroke or intracranial bleed, which cause central facial weakness (forehead sparing) and/or other focal deficits, BUT this patient has a classic peripheral palsy without other neurologic signs, making CT low yield.
Exam trap
The presence of vascular risk factors (hypertension, smoking) tempts you to think stroke and pick CT, but forehead involvement and recent New England outdoor exposure point instead to Lyme-related Bell palsy, where the correct next step is serologic ELISA, not neuroimaging.
The bottom line
Lyme disease–associated Bell palsy after New England outdoor exposure → diagnose with two-step serology: ELISA first, then Western blot confirmation.
A 32-year-old man presents with 8 days of dysuria and, on awakening this morning, noticed a clear urethral discharge. He reports no chronic medical conditions. He works on a local farm with livestock. Over the past week, he has also developed pain in his left knee and ankle and has had worsening seasonal allergies with red, itchy eyes. Temperature is 36.5°C (97.7°F), blood pressure is 122/83 mm Hg, pulse is 89/min, respirations are 14/min, and oxygen saturation is 98% on room air. Which of the following is likely to be positive in this patient?
Correct answer · C
HLA-B27
Decoding the stem
Step-by-step reasoning
Step 1 of 5
The patient has clear urethral discharge and dysuria → indicates urethritis, often due to Chlamydia or other GU infections.
Step 2 of 5
He develops acute knee and ankle pain shortly after the urethritis → points to a postinfectious inflammatory arthritis rather than degenerative disease.
Step 3 of 5
He also has red, itchy eyes compatible with conjunctivitis → now we have urethritis + arthritis + conjunctivitis.
Step 4 of 5
The triad of urethritis, conjunctivitis, and arthritis is classic for reactive arthritis (Reiter syndrome), a seronegative spondyloarthropathy.
Step 5 of 5
Seronegative spondyloarthropathies (including reactive arthritis) are strongly associated with HLA-B27 → this is the marker most likely to be positive.
Why not the others?
A. Anti-CCP
This option implies rheumatoid arthritis, which causes chronic, symmetric small-joint polyarthritis of hands/feet, BUT this patient has acute, asymmetric large-joint arthritis with preceding urethritis and conjunctivitis.
B. Anti-dsDNA
This option implies systemic lupus erythematosus, which causes malar rash, photosensitivity, cytopenias, and nephritis, BUT the patient’s presentation is dominated by postinfectious arthritis and urethritis without systemic lupus features.
D. HLA-DR4
This option implies rheumatoid arthritis association, leading to chronic symmetric inflammatory arthritis, BUT the vignette shows a reactive, postinfectious triad (urethritis, conjunctivitis, arthritis) more consistent with a seronegative, HLA-B27–linked process.
E. p-ANCA
This option implies MPO-ANCA–associated vasculitis (e.g., microscopic polyangiitis) or sometimes ulcerative colitis, which cause systemic vasculitic signs (hematuria, pulmonary hemorrhage), BUT no vasculitis, GI, or pulmonary features are described here.
Exam trap
The presence of urethral discharge may push you to think purely infectious (e.g., STI workup) and ignore the concurrent arthritis and eye symptoms. Recognizing the classic triad of reactive arthritis is key, then recalling its HLA-B27 association rather than defaulting to more common autoimmune markers (RF, anti-CCP, ANA, p-ANCA).
The bottom line
Reactive arthritis (post-urethritis triad: arthritis, conjunctivitis, urethritis) is strongly associated with HLA-B27 positivity.
A 16-year-old boy who recently immigrated from Nigeria to the United States for a year of high school is brought to the physician by his host parents due to a 6-month history of a progressively pruritic rash over his shoulders and buttocks. He also reports increasing difficulty reading the whiteboard in class. Physical examination reveals symmetrically distributed 4–8 mm papules with excoriations and patchy hyperpigmentation over the shoulders, waist, and buttocks. There is nontender inguinal lymphadenopathy and several firm, nontender subcutaneous nodules along the right iliac crest. Six skin snip biopsies from the pelvic girdle, buttocks, and thigh are incubated in saline, and microscopic examination after 24 hours reveals motile microfilariae. Which of the following is the most likely diagnosis?
Correct answer · B
Onchocerciasis
Decoding the stem
Step-by-step reasoning
- 1
The patient is from Nigeria, an endemic region for Onchocerca volvulus transmitted by blackflies near rivers.
- 2
He has a chronic, intensely pruritic papular rash with hyperpigmentation over buttocks/waist/shoulders, classic distribution for onchodermatitis.
- 3
Presence of firm, nontender subcutaneous nodules indicates fibrous nodules (onchocercomas) harboring adult worms.
- 4
He reports progressive visual difficulty, consistent with microfilariae migrating to the eye, causing keratitis and eventual river blindness.
- 5
Definitive diagnostic clue: skin snip biopsies showing motile microfilariae after incubation in saline, which is characteristic of Onchocerca volvulus.
- 6
Combining endemic region + pruritic papular rash + nodules + vision changes + skin-snip microfilariae → diagnosis is onchocerciasis.
Why not the others?
A. Lymphatic filariasis
This option implies Wuchereria bancrofti/Brugia infection causing lymphatic obstruction and lymphedema/elephantiasis, BUT this patient has pruritic skin papules, nodules, and eye symptoms without massive limb or scrotal swelling.
C. Trichuriasis
This option implies Trichuris trichiura (whipworm), which causes GI symptoms (diarrhea, rectal prolapse) and eosinophilia, BUT the patient has dermatologic and ocular findings with skin-snip microfilariae, not intestinal worms.
D. Cysticercosis
This option implies Taenia solium larval infection causing neurocysticercosis (seizures, CNS cysts) or muscle nodules, BUT the key diagnostic test here is skin snip microfilariae, and the main features are pruritic rash and visual changes, not seizures or intracranial lesions.
E. Cutaneous larva migrans
This option implies Ancylostoma hookworm larvae causing serpiginous, intensely pruritic tracks on feet/areas contacting sand, BUT this patient has symmetric papules, subcutaneous nodules, and ocular involvement, not migrating linear skin tracks.
Exam trap
The presence of microfilariae may push students toward any filarial disease (e.g., lymphatic filariasis). To avoid this, anchor on the specific triad: chronic pruritic papular rash + subcutaneous nodules + progressive visual impairment in a West African patient → onchocerciasis, not Wuchereria-related elephantiasis.
The bottom line
Onchocerciasis (Onchocerca volvulus) from blackfly bites → pruritic papular rash, subcutaneous nodules, microfilariae in skin snips, and progressive vision loss (“river blindness”).
Source: StepGenie question bank. Questions are written by StepGenie, not taken from NBME or USMLE materials, and are chosen for this page by how students actually performed on them (first-attempt accuracy on StepGenie). Selection last refreshed September 5, 2026.
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Comprehensive review of bacteria, viruses, fungi, and parasites. Learn infection patterns, antimicrobial mechanisms, resistance patterns, and approach to fever of unknown origin.
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Infectious Disease — Frequently Asked Questions
How do you choose the likely organism from a vignette?
Let the host and the setting narrow it before the symptoms do. Age, immune status, recent hospitalisation, travel, animal exposure and indwelling devices each map to a short list of organisms. Then use the site of infection and Gram stain. Most exam questions are solvable from exposure history plus one laboratory clue.
What are the most testable meningitis findings on CSF?
Bacterial meningitis gives high neutrophils, high protein and low glucose. Viral meningitis gives lymphocytes, mildly high protein and normal glucose. Fungal and tuberculous meningitis give lymphocytes with high protein and low glucose. The glucose level is the fastest discriminator, because low glucose indicates organisms consuming it.
Which HIV opportunistic infections are tied to specific CD4 counts?
Below two hundred, Pneumocystis jirovecii pneumonia becomes the concern and prophylaxis begins. Below one hundred, toxoplasmosis and cryptococcal disease enter the differential. Below fifty, Mycobacterium avium complex and cytomegalovirus retinitis appear. The CD4 count in the stem is usually placed there to point you at a specific organism.
How should you think about antibiotic selection questions?
Match spectrum to the likely organism and site rather than memorising drug lists. Know which agents cross the blood-brain barrier, which cover Pseudomonas, which cover anaerobes, and which cover MRSA. Exam questions frequently test a contraindication instead, such as avoiding fluoroquinolones and tetracyclines in children and pregnancy.
Are the infectious disease practice questions on this page free?
Yes. The 5 questions above come from StepGenie's question bank and can be answered here without an account, with the full explanation shown after each one. From the link under the set you can try three more Infectious Disease questions in the dashboard preview, also without an account; a free account is what lets you choose the system and keep going.