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USMLE Step 1 High‐Yield Microbiology Topics

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Microbiology

High Yield USMLE Step 1 Notes

Welcome to the Microbiology High-Yield Notes for Step 1.

These are the most commonly tested topics on the exam—ideal for quick review in your last 2 weeks before the exam, when you’re short on time, or when you’re just starting out and want to focus on what is high yield. Created and peer-reviewed by physicians who scored 260+ on Step 1 in a Q&A style to reinforce active learning.

How to use this file

Read the question ➔ cover the answer ➔ self-quiz before revealing.
Review the NOTES ➔ they include high-yield details you don’t want to miss.
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Don’t forget to watch the video lessons that go with this file. Learn more here.

Bacteria

1. A 5 year old child presents with itchy, honey-colored crusts around the mouth and nose, along with bullous lesions. What is the causative organism?
➔ Staph aureus (symptoms suggestive of Bullous Impetigo → caused by Staph aureus)

Note: Comparison of Non-bullous vs. Bullous Impetigo

Feature	Non-bullous Impetigo	Bullous Impetigo
Cause	Strep pyogenes (GAS) or Staph aureus	Staph aureus
Toxin Involved	not toxin-mediated	Exfoliative toxin A/B
Lesion Appearance	Honey-colored crusts without bullae	Flaccid bullae that rupture easily

Vs. Herpes simplex (HSV) which presents with:
→ Painful grouped vesicles on erythematous base
→ +Tzanck smear.

Vs. Contact dermatitis which presents with:
→ Linear/geometric pruritic plaques with no crusts/bullae
→ History of allergen exposure.

2. A 2-day-old neonate develops generalized erythema, tender skin peeling, and Nikolsky sign. No mucosal involvement. What is the key toxin responsible?
➔ Exfoliative toxin (It is produced by Staphylococcus aureus → cleaves desmoglein-1 → leading to Staphylococcal Scalded Skin Syndrome)

Note: Staphylococcal Scalded Skin Syndrome (SSSS):
→ Has no mucosal involvement as desmoglein-3 which is found in mucosa → is not affected
→ Has + Nikolsky sign which means that gentle pressure causes skin to slough off.

Differential Diagnosis:

Condition	Key Features	Toxin/Cause
SSSS	→ Neonates with tender erythema, superficial desquamation → no mucosal involvement → +Nikolsky	Exfoliative toxin (Staph aureus)
Toxic Epidermal Necrolysis (TEN)	→ Drug-induced (e.g., sulfa, anticonvulsants) → mucosal involvement and full-thickness epidermal necrosis → +Nikolsky	Delayed type IV hypersensitivity
Toxic Shock Syndrome (TSS)	→ High fever, hypotension, diffuse rash → desquamation (esp. palms/soles), mucosal hyperemia (e.g., strawberry tongue) → hx of tampon/nasal packing	TSST-1 (superantigen from Staph aureus)

3. A 5 year old child presents with acute pharyngitis, high fever, and swollen tonsils with exudate. The rapid antigen test is positive. What is the key virulence factor of the causative organism?
➔ M protein (symptoms suggestive of Streptococcal pharyngitis which is → caused by Streptococcus pyogenes (Group A Strep, GAS))

Note: Key virulence factor for GAS is M protein:
→ It is anti-phagocytic
→ Causes Molecular mimicry as it Shares structural similarity with cardiac myosin → leading to autoimmune cross-reactivity → causing Rheumatic fever

Compare with:

Organism	Virulence Factor	Function
Strep pyogenes (GAS)	M protein	Anti-phagocytic, molecular mimicry → rheumatic fever
Staph aureus	Protein A	Binds Fc portion of IgG → inhibits opsonization & phagocytosis

4. 46 year old woman presents with progressive orthopnea (now requiring 2 pillows), rusty-colored sputum, and a mid-diastolic rumbling murmur. Echo reveals mitral stenosis with left atrial dilation. What is the underlying cause?
➔ Recurrent group A streptococcal infections (Symptoms suggestive of Rheumatic Mitral Stenosis)

Note: Rheumatic heart disease
→ Sequelae of untreated/recurrent Group A Streptococcal (GAS) pharyngitis → leading to acute rheumatic fever → causing chronic rheumatic heart disease
→ Mitral valve most commonly affected → leads to stenosis.
→ Histopathology shows Aschoff bodies (perivascular granulomas with Anitschkow cells)

5. A 28-year-old woman with a history of rheumatic fever and mitral regurgitation presents with 2 weeks of fever, fatigue, and a new diastolic murmur at the apex. She underwent a dental procedure 4 weeks ago. What is the causative organism?
➔ Streptococcus mitis (viridans group streptococci) (it can cause subacute endocarditis in patients with damaged valves, especially after dental work)

Note: Key Features of Subacute Endocarditis:
→ Indolent symptoms (weeks of fever, fatigue)
→ Predisposing factors include Rheumatic heart disease, dental procedures
Differential Diagnosis: Acute vs Subacute Endocarditis

Feature	Subacute (Viridans strep)	Acute (Staph aureus)
Onset	Weeks	Rapid (days)
Valve type	Previously abnormal (e.g. rheumatic)	Normal or abnormal
Murmur	New or changing murmur	Often tricuspid regurgitation (IV drug use)
Organism	Viridans streptococci (S. mitis, S. sanguinis)	Staph aureus

Microbiology facts of Viridans streptococci (e.g., S. mitis, S. sanguinis):
→ Alpha-hemolytic, optochin-resistant, bile-insoluble
→ Prophylaxis is required before dental work in high-risk patients with Amoxicillin.

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6. A 65-year-old man is diagnosed with subacute endocarditis. Blood cultures grow Gram-positive cocci in chains. Further evaluation reveals a mass in his colon. What is the organism?
➔ Streptococcus gallolyticus (Endocarditis + colon cancer → Think S. gallolyticus)

Note: Part of normal gut flora; enters bloodstream via mucosal breaks (e.g., tumor)
Causes subacute endocarditis with strong link to colon cancer or polyps
If found → always screen for colorectal cancer

7. A 6-year-old unvaccinated child presents with sore throat, low-grade fever, and a thick gray coating on the pharynx. He later develops arrhythmia and signs of heart failure.What is the causative organism?
➔ Corynebacterium diphtheriae (It produces a toxin that inhibits EF-2 → leading to pseudomembrane formation and myocarditis)

Note: Myocarditis is major cause of death → due to diphtheria exotoxin
→ Mechanism: Toxin inactivates EF-2, halting protein synthesis → leading to tissue necrosis and ↑ cAMP → causing systemic toxicity
Prevented by DTaP vaccine (toxoid vaccine)

8. A 65 year old smoker with no spleen presents with rust-colored sputum and abrupt fever. CXR shows lobar consolidation. What is the key virulence factor of the causative organism?
➔ Polysaccharide capsule (Symptoms suggestive of → Lobar pneumonia due to Streptococcus pneumoniae → which has Polysaccharide capsule as a virulence factor)

Note: S.pneumoniae is → the most common cause of lobar pneumonia
Polysaccharide capsule is key virulence factor:
→ It prevents phagocytosis by neutrophils and alveolar macrophages.
→ Particularly dangerous in asplenic patients due to impaired clearance of encapsulated organisms (Loss of IgM-mediated opsonization → ↑ risk of encapsulated infections)
Mnemonic: SHiN organisms – encapsulated bacteria that cause severe infections in asplenic patients:

Organism	Disease Associations
Streptococcus pneumoniae	Pneumonia, meningitis
Haemophilus influenzae type b	Epiglottitis, Pneumonia, meningitis
Neisseria meningitidis	Meningitis, sepsis

9. A vaccine is being developed against Streptococcus pneumoniae by conjugating its capsular polysaccharide to a bacterial component. Which type of component should be used to enhance immunogenicity?
➔ Protein (conjugating polysaccharides to a protein carrier elicits a T-cell–dependent immune response improving → class switching, memory B-cell formation, and long-term immunity.)

Note: Protein carriers like flagellin or diphtheria toxoid are used to conjugate polysaccharides and enhance immune response by triggering T-cell help.

10. A 72 year old nursing home resident with dementia and dysphagia develops fever, cough with foul-smelling sputum, and right lower lobe infiltrate on CXR after a witnessed aspiration event. Sputum culture grows anaerobic Gram-negative rods. What is the pathogen?
➔ Bacteroides fragilis (It is a common anaerobe in aspiration pneumonia, especially in an elderly with risk factors)

Note: Aspiration pneumonia is common in patients with:
→ Altered consciousness (dementia, stroke, alcohol use), Dysphagia or GERD
→ Usually affects dependent lung zones → Right lower lobe (RLL) > LLL due to bronchial anatomy
Cultures often grow oral anaerobes: Bacteroides, Fusobacterium, Peptostreptococcus
Empiric Treatment:
→ Clindamycin (inhibits 50s subunit translocation)
→ or piperacillin-tazobactam (β-lactam/β-lactamase inhibitor)
Differential Diagnosis:

Pathogen	Key Features
Streptococcus pneumoniae	Sudden onset, rusty sputum, no foul odor
Klebsiella pneumoniae	Currant jelly sputum, upper lobe infiltrate
Mycobacterium tuberculosis	Night sweats, apical infiltrates, AFB+

11. A 27-year-old man with severe burns develops fever, hypotension, and greenish-blue pus at the wound site. Gram stain shows motile gram-negative rods. What is the causative organism?
➔ Pseudomonas aeruginosa (It is a common cause of burn wound infections and produces blue-green pigment and fruity odor)

Note: Gram-negative, aerobic, motile rod
Produces Exotoxin A → inhibits EF-2 (similar to diphtheria toxin)

Condition	Mechanism/Clue
Burn wound infection	Blue-green pus, fruity smell
Ecthyma gangrenosum	Necrotic skin lesion in neutropenia
Otitis externa (“swimmer’s ear”)	Water exposure, pain on pinna pull
Cystic fibrosis pneumonia (chronic)	Biofilm formation, mucoid colonies

Treatment:
→ Anti-pseudomonal β-lactams (e.g., piperacillin-tazobactam, cefepime, ceftazidime, meropenem)
→ Add aminoglycoside or fluoroquinolone in severe cases

12. A 30-year-old pregnant woman presents with fever, myalgias, and malaise after eating soft cheese and refrigerated deli meats. Blood cultures grow a Gram-positive rod with tumbling motility that grows at 4°C. What is the organism?
➔ Listeria monocytogenes (It is an intracellular pathogen that causes flu like illness in pregnant women)

Note: Listeria monocytogenes:
○ Gram (+) rod with tumbling motility
○ Treat with ampicillin

Clinical Presentations of Listeria monocytogenes by Patient Population

Population	Clinical Presentation	Key Features
Healthy adults	Often asymptomatic or mild gastroenteritis	Fever, diarrhea, nausea
Pregnant women	Flu-like illness	Fever, myalgias, malaise, risk of miscarriage and fetal infection
Fetus	Granulomatosis infantiseptica	Widespread abscesses and granulomas
Neonates (late onset)	Meningitis and sepsis	Postnatal infection
Immunocompromised/elderly	Meningitis, encephalitis (rhombencephalitis), sepsis	Headache, stiff neck, altered mental status

13. A 9-day-old neonate presents with fever and a bulging anterior fontanelle. Gram stain of CSF shows gram-negative rods. Lumbar puncture confirms E. coli meningitis. What is the key virulence factor?
➔ K1 capsule (Its is a key virulence factor of E. coli that prevents phagocytosis and Facilitates crossing the blood-brain barrier → leading to neonatal meningitis)

E. coli Pathotypes & Virulence Factors Summary:

E. coli Pathotype	Virulence Factor	Associated Disease
Enterotoxigenic E. coli (ETEC)	Heat-labile toxin (1 cAMP), Heat-stable toxin (1 cGMP)	Traveler’s diarrhea (watery diarrhea)
Enterohemorrhagic E. coli (EHEC) O157:H7	Shiga-like toxin	Bloody diarrhea, Hemolytic Uremic Syndrome (HUS)
Uropathogenic E. coli (UPEC)	Pili (P fimbriae)	Urinary Tract Infection (UTI) (Cystitis, Pyelonephritis)
Neonatal Meningitis-causing E. coli	K1 Capsule	Neonatal Meningitis
Septicemia-causing E. coli	Endotoxin (Lipid A of LPS)	Septic Shock (Fever, hypotension, DIC)

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14. A 1-day-old boy is inconsolable, febrile, and has a bulging anterior fontanelle. What is the diagnosis?
➔ Neonatal meningitis (fever, irritability, and a bulging fontanelle indicate increased intracranial pressure from meningeal infection in a neonate)

Note: Bulging fontanelle is buzzword for elevated intracranial pressure (e.g. meningitis)
Common organisms: GBS, E. coli, Listeria monocytogenes
GBS & E. coli have capsules that → prevent phagocytosis
Empiric treatment: Ampicillin (for Listeria and Gram-positive coverage) + gentamicin (for Gram-negative coverage).

15. A 19-year-old college student presents with high fever, headache, neck stiffness, and a rapidly spreading purpuric rash. He becomes hypotensive and unresponsive within hours. What is the cause of his hemodynamic instability?
➔ Bilateral adrenal hemorrhage (Acute septic shock + meningitis + purpuric rash → think meningococcemia with adrenal crisis (Waterhouse-Friderichsen syndrome))

Note: N. meningitidis (Gram -ve diplococci) can causes → meningitis + sepsis in young adults
Waterhouse-Friderichsen Syndrome:
→ is a life-threatening complication of meningococcemia (driven by endotoxins)
→ Characterized by bilateral adrenal hemorrhage → leading to acute adrenal insufficiency
→ Presents with sudden hypotension, shock, DIC, and purpuric rash.

16. A 5 year old child develops bloody diarrhea and oliguria 1 week after eating undercooked meat. The lab shows thrombocytopenia, schistocytes on peripheral smear, and elevated creatinine. What is the causative pathogen?
➔ EHEC (Enterohemorrhagic E. coli)- serotype O157:H7( It Causes Shiga-like toxin-mediated endothelial damage → leading to Hemolytic Uremic Syndrome (HUS))

Note: EHEC leads to Hemolytic Uremic Syndrome triad:
○ Microangiopathic hemolytic anemia (schistocytes)
○ Thrombocytopenia
○ Acute kidney injury
Avoid antibiotics – they can increase toxin release and worsen HUS.
Differential Diagnosis:

Condition	Key Features
EHEC (O157:H7)	Bloody diarrhea after beef ingestion,no fever ; risk of HUS (anemia + thrombocytopenia + AKI)
Shigella dysenteriae	Bloody diarrhea, fever, WBCs in stool, Shiga toxin, also causes HUS
Enteroinvasive E.coli	Dysentery-like illness with fever + WBCs in stool; invades intestinal mucosa like Shigella, but no toxin
Campylobacter jejuni	Bloody diarrhea + fever, risk of Guillain-Barré syndrome

17. A 22 year-old backpacker develops watery diarrhea 2 days after arriving in Mexico. He reports no blood/mucus in stool and no fever. What is the causative pathogen?
➔ Enterotoxigenic E. coli (ETEC) (It Produces heat-labile (LT) and heat-stable (ST) enterotoxins → ↑ cAMP/↑ cGMP → secretory diarrhea)

Note: Non-bloody + afebrile + watery diarrhea in endemic areas (e.g., Latin America, Africa) → think ETEC (Traveler’s diarrhea)
It is typically self-limiting (3-5 days)
Differential Diagnosis:

Condition	Key Features
Vibrio cholerae	Profuse “rice-water” diarrhea, severe dehydration, often epidemic-related
Giardia lamblia	Chronic steatorrhea, bloating, often >1 week, associated with camping/water exposure

18. A 22 year old man develops nausea, cramping abdominal pain, and diarrhea 24 hours after eating at a wedding reception. Stool culture grows Salmonella. Symptoms resolve within 36 hours but persist mildly for days. What is the complication if treated with antibiotics?
➔ Prolonged fecal excretion of the organism (Antibiotic use in Salmonella can → disrupt normal gut flora → leading to prolonged the carrier state → leading to Prolonged fecal shedding)

Note: Key Features of Salmonella Gastroenteritis:
→ Transmitted by undercooked poultry, eggs, contaminated food/water
→ Self-limiting in immunocompetent hosts
Other complications Salmonella Gastroenteritis:
→ Reactive arthritis (post-infectious, autoimmune): “Can’t see (uveitis), can’t pee (urethritis), can’t climb a tree (arthritis)”
→ Osteomyelitis in sickle cell disease patients (Salmonella is a classic cause)

19. A 45 year old woman with chronic alcohol use disorder presents with fever , malaise, and abdominal distension. Exam shows spider angiomas, shifting dullness, and a firm liver edge. Paracentesis reveals 1100 WBCs/mm³ (60% PMNs). What is the causative organism?
➔ Escherichia coli (Symptoms suggestive of Spontaneous Bacterial Peritonitis which is caused by E. coli translocating across the intestinal wall into ascitic fluid in cirrhotic patients)

Note: Spontaneous Bacterial Peritonitis:
→ PMN count ≥250 cells/mm³ in ascitic fluid → is Diagnostic
→ Escherichia coli is the most common causing organism
→ Treatment: Ceftriaxone

20. A 32-year-old man develops ascending weakness and paresthesia 2 weeks after Campylobacter gastroenteritis. He has areflexia, bilateral foot drop, and normal mental status. CSF shows ↑ protein, normal WBC count. What is the diagnosis?
➔ Guillain-Barré syndrome (GBS) (Infection followed by → ascending weakness and paresthesia → think Guillain-Barré syndrome)

Note: It is post-infectious demyelination of peripheral nerves
Diagnosed by nerve conduction studies which shows → slowed conduction velocities (demyelination)
Treatment:
→ IVIG or plasmapheresis. NO ROLE FOR CORTICOSTEROIDS.
→ Monitor for respiratory failure (may need intubation)

Pathogenesis and Clinical Features of Guillain-Barré Syndrome

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21. A 64-year-old woman develops abdominal pain and profuse watery diarrhea after recent clindamycin use. Stool toxin assay is positive. What is the cause?
➔ Clostridium difficile infection (Hospitalized or elderly patient who develops diarrhea following antibiotic use → think Clostridium difficile)

Note: Diagnosis: C. diff toxin A/B in stool (PCR or ELISA)
Classic Findings: Watery diarrhea ± pseudomembranes on colonoscopy
Treatment:
→ First-line: Oral vancomycin (stays in gut → effective locally)
→ Alternative: Fidaxomicin

22. A 50-year-old with epigastric pain has a positive urea breath test. How does this organism survive stomach acid?
➔ Urease production (Symptoms suggestive of H. pylori which produces Urease which → breaks down urea into ammonia → neutralizing stomach acid)

Note: Untreated H. pylori leads to MALT Lymphoma.
Other Urease-Positive Organism is Proteus → causes UTIs and struvite stone

23. An experiment is done exposing guinea pigs to food containing Clostridium botulinum toxin. One guinea pig does not develop symptoms. Serum shows high antibody titers. Which bacterial product is targeted by the antibodies?
➔ Exotoxin (Botulinum toxin is a secreted protein that can be neutralized by antibodies)

Note: Botulinum toxin is an exotoxin (NOT endotoxin)

Comparison of Exotoxins vs Endotoxins

Feature	Exotoxin	Endotoxin (LPS)
Source	Gram+ (e.g., Clostridium)	Gram− only
Composition	Protein (secreted)	Lipid A (outer membrane)
Immune Rxn	Neutralized by antibodies	Activates macrophages → TNF/IL-1
Examples	Botulinum, Tetanospasmin	E. coli LPS

24. A 35-year-old man with HIV develops diffuse lymphadenopathy, hepatosplenomegaly, and constitutional symptoms. What is the diagnosis?
➔ Miliary tuberculosis (Occurs due to hematogenous spread of Mycobacterium tuberculosis in immunocompromised patients like HIV+)

Note: Primary TB: Initial infection in mid/lower lobes → forms Ghon focus + hilar LAD (Ghon complex) → Most heal with fibrosis and may remain latent.
Secondary TB: Reactivation (e.g., due to immunosuppression, anti–TNF-α therapy) → affects Upper lobes (↑O₂) → causing cavitary lesions
→ Classic symptoms: Fever, night sweats, cough, hemoptysis, weight loss.
Miliary TB: Disseminated TB due to hematogenous spread → involves multiple organs.

Pathogenesis and Progression of Pulmonary and Extrapulmonary Tuberculosis

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25. A 25 year old immigrant from a TB-endemic region presents with chronic back pain, night sweats, and progressive kyphosis. MRI reveals vertebral body destruction with a paraspinal abscess. What is the diagnosis?
➔ Pott’s disease (Caused by Mycobacterium tuberculosis spread hematogenously from a primary site (often lungs) → leading to spinal tuberculosis(Pott’s disease))

Note: Think of TB if the patient is an immigrant from a developing country (e.g. India, Africa) or has a history of HIV, homeless or imprisoned.

Differential Diagnosis:

Condition	Key Features
Pott’s disease	Gradual, systemic symptoms, paraspinal abscess, endemic risk
Metastatic cancer	Osteolytic/blastic lesions, older age, no systemic infection signs
Pyogenic osteomyelitis	Rapid onset, high fever, ↑ WBC, localized tenderness

26. A patient with fever, night sweats and weight loss underwent sputum analysis, which shows acid-fast bacilli. What’s the virulence factor of this organism?
➔ Cord factor.(It inhibits macrophage maturation and triggers TNF-α release → aiding granuloma formation)

Note: Cord factor = virulence factor of Mycobacterium tuberculosis
Cord factor inhibits macrophage maturation + stimulates TNF-α → leading to granuloma formation
M. tuberculosis is acid-fast due to its mycolic acid-rich cell wall
Isoniazid (INH) inhibits mycolic acid synthesis → impairing TB cell wall formation

27. Bacterial infection leads to cytokine release. Which receptor on neutrophils recognizes lipopolysaccharide (LPS), a PAMP, to trigger this response?
➔ Toll-Like Receptor 4 (TLR4) (TLR4 is the primary receptor for LPS, triggering NF-κB activation and cytokine production)

Note: LPS binding to TLR4 → activates NF-κB → transcription of pro-inflammatory cytokines: TNF-α, IL-1, IL-6
CD14 acts as a co-receptor with TLR4 to enhance LPS recognition and signal transduction
Overactivation of TLR4 by LPS (from Gram− bacteria) can trigger excessive cytokine release, leading to systemic inflammation and septic shock.

28. A 25 y old woman presents with thin, grayish-white vaginal discharge and a strong fishy odor noticed after intercourse. Pelvic exam shows homogeneous discharge coating the vaginal walls. What is the diagnosis?
➔ Bacterial vaginosis (Caused by overgrowth of Gardnerella vaginalis)

Note: Bacterial vaginosis is not sexually transmitted, but recurrence is associated with sexual activity.
Vaginal PH, discharge color are important for Diagnosis.
Compare Vaginal Infections (These conditions do not cause PID or genital ulcers):

Condition	Discharge & Characteristics	Diagnostic Findings	Vaginal pH
Bacterial Vaginosis	Thin, off-white, fishy odor (whiff test +)	Clue cells on microscopy	↑
Trichomoniasis	Yellow-green, frothy, foul-smelling	Motile trichomonads, strawberry cervix	↑
Candidiasis	Thick, white, “cottage cheese“-like	Pseudohyphae on KOH prep	N

29. A 24-year-old woman develops fever, chills, and lower abdominal pain during menstruation with adnexal tenderness and leukocytosis. What is the most likely causative organism?
➔ Neisseria gonorrhoeae (Fever + lower abdominal pain + cervical motion tenderness → think Pelvic Inflammatory Disease → Neisseria gonorrhoeae is the most likely causative organism)

Note: Common Causes of Pelvic Inflammatory Disease:

Feature	Neisseria gonorrhoeae	Chlamydia trachomatis
Gram stain?	Gram-negative diplococci	Not seen (intracellular)
Symptoms	More acute and systemic	Often mild or silent
PID severity	Higher	Lower
Common in co-infection?	Yes	Yes

NAAT (Nucleic Acid Amplification Test) is Gold standard for N. gonorrhoeae & Chlamydia
Treatment:
→ Ceftriaxone IM (for N. gonorrhoeae) + Doxycycline (for Chlamydia coverage)

On USMLE, Toxic Shock Syndrome often mimics PID, but look for
→ Tampon use
→ Rash + hypotension
→ Systemic involvement without localized pelvic pain

30. A 30 year old sexually active male presents with multiple painful, soft, non-indurated genital ulcers with ragged, undermined edges and purulent bases. Associated tender inguinal lymphadenopathy is present. What is the diagnosis?
➔ Chancroid (It is caused by Haemophilus ducreyi)

Note: Differential Diagnosis of Genital Ulcers:

Disease	Causative agent	Primary lesion	Painful?	Other Features
Chancroid	Haemophilus ducreyi	Multiple soft ulcers with ragged edges, purulent base	Yes	Painful inguinal lymphadenopathy
Genital Herpes	HSV-1 or HSV-2	Vesicles → painful shallow ulcers	Yes	Systemic symptoms common
Syphilis	Treponema pallidum	Single, indurated, well-circumscribed ulcer. No exudate	No	Painless, with painless lymphadenopathy
LGV (L1-L3)	Chlamydia trachomatis	Small & shallow ulcers – Painful inguinal lymph node	No	Painful inguinal lymphadenopathy (buboes), may suppurate

31. A 28-year-old man presents with a painless genital ulcer that developed two weeks ago. Physical exam shows a non-tender ulcer on the penis. Darkfield microscopy of the lesion reveals motile spirochetes. What is the diagnosis?
➔ Syphilis (Painless chancre with motile spirochetes on darkfield microscopy indicates → primary syphilis)

Note: Caused by Treponema pallidum (spirochete)
Clinical stages:
→ Primary: Painless chancre
→ Secondary: Maculopapular rash (involving palms/soles), condyloma lata
→ Tertiary: Neurosyphilis, gummas, aortitis

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32. A 10-year-old boy from Connecticut presents with fever and a red, expanding rash with central clearing on his thigh after a hiking trip. What is the causative organism?
➔ Borrelia burgdorferi (The classic erythema migrans rash after a tick bite in an endemic area is pathognomonic for early Lyme disease → caused by Borrelia burgdorferi)

Note: Vector: Ixodes tick (also transmits Babesia, Anaplasma)
Endemic: Northeast & Upper Midwest US
Treatment: Doxycycline (or amoxicillin if <8 y/o or pregnant)

Stages of Lyme Disease:

Stage	Features
Early localized	Erythema migrans (bull’s-eye rash), flu-like symptoms
Early disseminated	Multiple EM lesions, facial nerve palsy (Bell’s palsy), migratory arthritis, AV block
Late disseminated	Chronic arthritis, encephalopathy, neuropathy

33. A 7-year-old boy returns from a camping trip in North Carolina with high fever, headache, and a petechial rash that started on his wrists and ankles, spreading centrally. What is the causative organism?
➔ Rickettsia rickettsii (Tick exposure + fever + centripetal rash involving palms/soles → classic Rocky Mountain Spotted Fever)

Note: Obligate intracellular Gram-negative
Rash: starts on wrists/ankles → spreads to trunk, palms, soles
Labs: thrombocytopenia, ↑ LFTs, hyponatremia
Treat with doxycycline

34. A 32-year-old woman, recently out of a long-term relationship, is now sexually active with new partners. Physical exam is normal. What is the most important preventive counseling to provide?
➔ Condom use (Consistent Condom use → significantly reduces transmission of STIs)

Note: Use condoms with all new partners until mutual monogamy and negative STI screening are confirmed.
In case of high risk patient as one with new or multiple sexual partners → Recommend full STI panel for: HIV, Syphilis , Gonorrhea & Chlamydia and Hepatitis B (if risk factors present)

35. A 62-year-old man presents with acute onset left knee pain, swelling, and inability to bear weight. Joint aspiration reveals cloudy synovial fluid with WBC count of 75,000/mm³ (90% neutrophils). What is the diagnosis?
➔ Septic arthritis

Note: Synovial Fluid WBC Clues & Differential Diagnosis

Synovial WBC Count	Interpretation	Common Causes
>50,000/mm³, PMN > 75%	Septic arthritis (bacterial)	Staphylococcus aureus, Neisseria gonorrhoeae
10,000–50,000/mm³	Inflammatory arthritis	Lyme disease, viral arthritis
<10,000/mm³	Non-inflammatory arthritis	Rheumatoid arthritis (RA), osteoarthritis (OA)

Key Associations:
→ Gonococcal: Migratory polyarthralgia + dermatitis
→ Lyme disease: History of skin rash ‘ Erythema migrans’

VS Crystal Arthritis:
→ Gout → negatively birefringent crystals (needle-shaped)
→ Pseudogout → positively birefringent crystals (rhomboid-shaped)

36. A 25 year old sexually active male presents with acute onset right knee pain, swelling, and fever. Joint aspiration reveals cloudy synovial fluid with 50,000 WBCs/mm³ (90% PMNs) and Gram-positive cocci in clusters. What is the causative organism?
➔ Staphylococcus aureus (symptoms suggestive of septic arthritis → Staphylococcus is the most common cause in general adults)

Note: Swelling + fever + elevated WBCs in synovial fluid (especially >50,000/mm) → is diagnostic of septic arthritis
Causative Organisms by Risk Group:

Risk Group	Likely Organism
General adults	Staphylococcus aureus
Prosthetic joint	Staph epidermidis
Sexually active (<30 y)	Neisseria gonorrhoeae (GN diplococci)
Sickle cell disease	Staphylococcus aureus, Salmonella (GN rods)
IV drug users	Staphylococcus aureus, Pseudomonas aeruginosa

37. A 50 year old woman with recurrent UTIs with severe right flank pain, fever, and hematuria. She was treated 3 weeks ago for a Proteus mirabilis UTI. CT reveals a large, branching renal stone. What is the stone’s composition?
➔ Struvite (magnesium ammonium phosphate) (Proteus infection + branching renal stone → think Struvite stone)

Note: Key Features of Struvite Stones:
→ Caused by recurrent UTI with urease-producing bacteria: Proteus, Klebsiella, Staphylococcus saprophyticus
→ Urease converts Urea → into Ammonia → leading to Alkaline urine (↑ pH)
→ Has Staghorn appearance on imaging
Differential Diagnosis of Kidney Stones

Type of Stone	Key Features
Struvite	pH > 7, infection with urease-producers, staghorn shape
Calcium oxalate	Most common overall, pH < 7, envelope-shaped crystals
Uric acid	Radiolucent, pH < 5.5, rhomboid/diamond-shaped crystals
Cystine	Hexagonal crystals, pH 6.5–7.5, autosomal recessive (cystinuria)

38. A 7 year old boy presents with mild fever, a painless papule on his right hand and tender and swollen axillary lymph nodes for 2 weeks. His family reports a new kitten scratched him. What is the diagnosis?
➔ Cat scratch disease (Bartonella henselae) (Painless papule + tender lymph node after cat scratch think → Bartonella henselae (Cat scratch disease))

Note: Typically there is no systemic symptoms like weight loss or night sweats
Biopsy shows Granulomas with stellate abscesses
Treatment: Azithromycin (inhibits 50 subunit)

Differential Diagnosis:

Feature	Cat scratch disease	Kaposi sarcoma
Lesion	Painless papule (scratch site)	Purple violaceous plaques/nodule
Lymph nodes	Tender, regional	Non-tender / generalized (of involved)
Risk factors	Cat exposure	HIV/AIDS, HHV8 infection

39. A 56-year-old woman with poor dentition presents with a painless, slowly enlarging mandibular mass. CT shows bony erosion and lymphadenopathy. Aerobic cultures are negative.What is the most likely organism?
➔ Actinomyces israelii (A slow-growing jaw mass with poor dentition and negative aerobic cultures → think Actinomycosis → Caused by Actinomyces israelii)

Note: Key Features of Actinomycosis:
→ Chronic, indolent infection
→ Risk factors: Dental caries/trauma + Immunocompromise (e.g., diabetes, steroids)
→ Causes Painless, slow-growing mass with mandibular/jaw involvement
→ Microscopy:
○ Gram-positive, anaerobic, branching filamentous rods
○ “sulfur granules” (yellow colonies of filamentous bacteria)
→ Treatment: Penicillin G

40. A 10-month-old infant develops fever (39.2°C), tachypnea, and grunting 3 days post-op for cleft palate repair. Lung exam reveals crackles and decreased breath sounds. WBC is 68,000/mm³ with 85% neutrophils (10% bands). What is the mechanism of leukocytosis?
➔ Leukemoid reaction (It is Accelerated release of cells from bone marrow postmitotic pool)

Note: Leukemoid Reaction is triggered by severe infection, inflammation or stress
Leukemoid Reaction vs. CML

Feature	Leukemoid Reaction	CML
WBC Count	>50,000/mm³	Often very high (>100,000/mm³)
Left Shift	Present (↑ bands, metamyelocytes)	Present
Blasts	Absent	May be present
Basophils	Normal	↑ Basophils
LAP Score	High (↑ neutrophil activity)	Low
Cytogenetics	None	t(9;22) BCR-ABL (Philadelphia)

41. A 8-day-old newborn presents with bilateral eye discharge and eyelid swelling. The infant was delivered vaginally, and the mother had no prenatal care.. What is the causative organism and its serotype group?
➔ Chlamydia trachomatis, serotypes D–K (Conjunctivitis 5–14 days after birth → think Neonatal conjunctivitis due to perinatal exposure)

Note: Neonatal conjunctivitis timing Clue:

Timing of onset	Likely Cause
Within hours (same day)	Chemical conjunctivitis(e.g., from silver nitrate, if used)
2–5 days (1st week)	Neisseria gonorrhoeae
5–14 days (1–2 weeks)	Chlamydia trachomatis

Chlamydia trachomatis Serotypes

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42. A 6-month-old infant presents with constipation, poor feeding, and hypotonia (“floppy baby”). Parents report giving the baby honey. What is the cause?
➔ Clostridium botulinum (Honey + floppy baby → Think infant botulism)

Note: Blocks ACh release at neuromuscular junction → descending flaccid paralysis
Infant botulism: Ingestion of spores (e.g., honey) → germinate in gut
Foodborne botulism (adults): Ingestion of preformed toxin, typically from improperly canned food

43. A 25-year-old man steps on a rusty nail and develops jaw stiffness, a fixed grin-like facial spasm, and severe backward arching of his body. What is the cause?
➔ Clostridium tetani (Puncture wound + jaw stiffness + facial spasm + body arching → Think Tetanus)

Note: Produces a toxin that blocks inhibitory signals in nerves → causes muscle stiffness and spasms
Classic signs: jaw tightness (“lockjaw”), grinning facial spasm, and severe muscle arching
Prevent with tetanus vaccine

44. A 50-year-old man with a crush injury to his leg develops sudden severe pain, swelling, and crepitus at the wound site. The skin is tense, discolored, and oozes foul-smelling fluid. What is the most likely cause?
➔ Clostridium perfringens (Trauma + rapid tissue destruction + gas in wound → Think Gas Gangrene)

Note: Causes gas gangrene: Rapid muscle necrosis with gas bubbles in tissue (crepitus); caused by alpha toxin (lecithinase)
Causes food poisoning: Reheated meat → transient watery diarrhea from enterotoxin

45. A surgical team prepares instruments for a patient with suspected Clostridium difficile infection. Which disinfectant is most effective against the vegetative cells and spores?
➔ Hydrogen peroxide or iodine-based solutions. (These agents can penetrate and disrupt the resistant spore coat, unlike alcohol or bleach)

Note: Key spore-formers:
→ Bacillus spp. (e.g., B. anthracis)
→ Clostridium spp. (e.g., C. perfringens, C. difficile)

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VIRAL

46. A 62-year-old diabetic woman presents for routine care and receives the seasonal influenza vaccine.Which viral protein is the primary target of protective antibodies?
➔ Hemagglutinin (HA)

Note: Influenza Virus – Key Proteins & Clinical Relevance:

Target	Function	Drug/Vaccine Action
Hemagglutinin (HA)	Binds to sialic acid for entry	Influenza vaccine → develops antibodies against HA
Neuraminidase (NA)	Facilitates viral release	Oseltamivir → inhibits NA, preventing viral spread
Viral Uncoating	Releases viral RNA into host cell	Amantadine → blocks uncoating (not widely used due to resistance)
Viral RNA Replication	Host machinery used to synthesize viral RNA	IFN-α → prevents viral replication

47. A 80-year-old nursing home resident presents with sudden-onset fever (39.4°C), myalgias, and cough. Several residents are affected. A neuraminidase inhibitor is prescribed. What viral process does this drug block?
➔ Release of virus from infected cells (Drugs like oseltamivir and zanamivir inhibit neuraminidase → preventing the virus from exiting infected host cells and spreading)

Note: Used early (within 48 hours) of symptom onset for maximum efficacy.

48. During a severe influenza outbreak, several previously healthy adults develop rapidly progressive pneumonia with high mortality. Genetic analysis reveals the virus contains RNA segments from both human and avian strains. What mechanism most likely led to this outbreak?
➔ Genetic shift (reassortment in segmented viruses)

Note: Genetic Shift causes sudden major change → leading to Pandemics.
Caused by reassortment of genome segments when two different viral strains co-infect the same host cell.
Genetic Drift causes slow minor change → leading to Seasonal epidemics.
Due to point mutations in viral genes, altering surface proteins (e.g. HA, NA in influenza).

Viral Evolution Mechanisms: Recombination (left) and Reassortment (right)

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49. A 5-month-old infant has recurrent infections, failure to thrive, and chronic thrush. Flow cytometry shows absent HLA-DR expression and marked CD4+ T cell depletion.
What is the diagnosis?
➔ Vertically transmitted HIV infection (Neonate + recurrent infections + CD4 lymphopenia → think HIV)

Note: Most common in perinatal/vertical transmission
Flow cytometry hallmark: ↓CD4+ T cells + absent HLA-DR
Start ART immediately: 2 NRTIs (e.g., abacavir + lamivudine) + 1 protease inhibitor or integrase inhibitor
Monitor for immune reconstitution inflammatory syndrome (IRIS) which is paradoxical worsening after ART due to restored immune response

50. A 27-year-old AIDS patient presents with memory loss, ataxia, and word-finding difficulty. MRI shows diffuse white matter hyperintensities. Biopsy reveals foamy macrophages. What is the diagnosis?
➔ HIV encephalopathy (AIDS patient + progressive cognitive decline + diffuse white matter changes without mass effect → HIV encephalopathy)

Note: Histology Key: Perivascular foamy macrophages
Differential Diagnosis — Key Differentiators:

Condition	MRI Findings	Key Feature
PML (JC virus)	Sharply demarcated white matter lesions, typically in parietal/occipital lobes	No enhancement or mass effect
Toxoplasmosis	Multiple ring-enhancing lesions with surrounding edema	Most common CNS mass lesion in AIDS
Primary CNS Lymphoma	Solitary ring-enhancing lesion, often periventricular	EBV-positive B-cell origin
Neurocysticercosis (Taenia solium)	Multiple cysts and calcifications, seizures	Endemic areas

51. A 36 year old HIV+ man (CD4 count 80/mm³) presents with fever, dry cough, and hypoxemia. Chest X-ray reveals bilateral interstitial infiltrates. Bronchoalveolar lavage shows owl’s eye inclusions in alveolar macrophages. What is the diagnosis?
➔ Cytomegalovirus (CMV) pneumonitis (It causes pneumonitis in severely immunocompromised patients (CD4 <100) and is diagnosed by characteristic “owl’s eye” inclusions)

Note: Risk groups: HIV (CD4 <100), transplant recipients and neonates
Treatment:
→ Valganciclovir (oral) or Ganciclovir (IV)
→ Acyclovir is NOT effective against CMV.

Differential Diagnosis of Pneumonia in Immunocompromised Patients;

Condition	CD4 Count	Key Features
CMV	<50 cells/mm³	Owl’s eye inclusions, gradual onset
PCP (Pneumocystis jirovecii)	<200 cells/mm³	Ground-glass opacities, dry cough, hypoxemia, (+ve) silver stain
Influenza virus	Any	Rapid onset fever, myalgia, URI symptoms; risk of secondary bacterial pneumonia

52. A 2-year-old boy presents with a barking cough, hoarse voice, and noisy breathing when inhaling. His symptoms began after a cold. Neck X-ray shows subglottic narrowing. What is the most likely cause?
➔ Parainfluenza virus (Barking seal-like cough + inspiratory stridor, worse at night → Think Croup)

Note: X-ray: Steeple sign = subglottic narrowing

53. A 15-year-old girl presents with fever, sore throat, and fatigue for 3 days. She has tender posterior cervical lymphadenopathy, exudative pharyngitis, WBC 19,500/mm³ with 30% atypical lymphocytes, and a positive heterophile antibody (Monospot) test. What virus causes this presentation?
➔ Epstein-Barr Virus (EBV) (Fever + sore throat + lymphadenopathy with atypical lymphocytosis → think infectious mononucleosis → caused by EBV)

Note: EBV Pathophysiology:
→ Infects B cells via CD21
→ Atypical lymphocytes seen on smear are reactive CD8+ T cells (not infected B cells!) → USMLE favorite point
EBV Diagnosis:
→ Monospot (heterophile antibody) test: Positive in EBV
→ If Monospot is negative, consider CMV or acute HIV (especially if symptoms persist or atypical)
Classic exam scenario:
→ a patient with sore throat is wrongly given amoxicillin then develops a diffuse maculopapular rash → suspect EBV (It is not an allergy, but a drug-related immune reaction in mono)

54. A 63-year-old man from southern China has had 5 months of bloody nasal discharge and a fixed, enlarged posterior cervical lymph node. Biopsy shows keratin-positive epithelial cells with EBV nuclear antigen. What oncogenic virus is associated with this malignancy?
➔ Epstein–Barr virus (EBV) (Symptoms suggestive of nasopharyngeal carcinoma, EBV is strongly linked to it especially in endemic regions like southern China.)

Note: Other EBV-Associated Cancers are Burkitt lymphoma, Hodgkin lymphoma and Primary CNS lymphoma (especially in immunocompromised patients)

55. A 2-month-old boy with hoarseness for 7 days is found to have a vocal cord nodule. His mother has AIDS. What is the viral cause?
➔ Human papillomavirus (HPV) (It Causes recurrent respiratory papillomatosis due to perinatal transmission during vaginal delivery.)

Note: Treatment:
→ Surgical excision (recurrence common)
Virus Preferences:
→ HPV → loves squamous epithelium (causes → oropharyngeal SCC, anal SCC, laryngeal papillomas)
→ EBV → loves respiratory epithelium (causes → nasopharyngeal carcinoma)

56. A 35-year-old woman presents with recurrent painful lip blisters. What neuronal process established the recurrent infection?
➔ Anterograde axon transport (Symptoms suggestive of HSV infection recurrence)

Note: HSV Pathway:
→ Infection occurs at mucosal surfaces then travels retrograde via dynein motors to sensory ganglia (e.g., trigeminal ganglion) → where it becomes latent.
→ During reactivation (e.g., stress, illness) the virus travels anterograde via kinesin back to the skin or mucosa → causing recurrent lesions.
Complications:
→ HSV-1 → classically causes encephalitis (affects the temporal lobe)
→ Aseptic meningitis.(especially with primary infection)
Another example is Tetanus toxin which uses retrograde transport to reach CNS and inhibit inhibitory neurons (↓ GABA, glycine)

57. A 56-year-old man presents with fever, headache, and painful penile ulcers 2 weeks after unprotected sex. Exam shows vesicular lesions and inguinal lymphadenopathy. What is the diagnosis?
➔ Genital herpes (HSV-2) (Painful fenital vesicles/ulcers + systemic symptoms after sexual contact → think HSV-2)

Note: Diagnosis:
→ PCR → Gold standard for diagnosis
→ Tzanck smear → shows multinucleated giant cells (it has low sensitivity)
Treatment:
→ Valacyclovir or famciclovir (better compliance than acyclovir due to longer half-life)
Complications:
○ Neonatal herpes if mother has active lesions during delivery

58. A 55-year-old man presents with a unilateral, painful, vesicular rash on his back in a band-like distribution. What is the diagnosis?
➔ Herpes zoster (shingles) (A painful, dermatomal vesicular rash appears in an older or immunocompromised patient → think shingles)

Note: Caused by reactivation of latent VZV (varicella-zoster virus) from dorsal root ganglia.
Prodrome: Pain, burning, or itching in the affected dermatome may precede the rash.
Lesion: Unilateral cluster of vesicles on an erythematous base in a dermatomal (band-like) pattern.

59. An 18-month-old HIV-positive boy in West Africa presents with hypoxia and diffuse interstitial infiltrates three weeks after contact with a febrile relative. He has no rash. Lung biopsy reveals multinucleated giant cells. Which pathogen is most likely responsible?
➔ Measles virus (In immunocompromised patients, measles may present without rash and cause giant cell pneumonia.)

Note: Giant Cell Pneumonia is a Severe, often fatal lung infection caused by measles virus in immunocompromised hosts
Typical Measles presentation is:
→ Prodrome: Fever, cough, coryza, conjunctivitis
→ Koplik spots (blue-white lesions on buccal mucosa) (Pathognomic)
→ Maculopapular rash spreading head-to-toe (may be absent in immunosuppressed)

Vitamin A deficiency increases measles severity and mortality
Prevention:
→ MMR vaccine (Live attenuated) (contraindicated in HIV+CD <200)
→ Immune globulin as Post-exposure prophylaxis for exposed immunocompromised patients

60. A 16-year-old boy presents with swelling near his jaw, pain in his testicles, and a headache. He recently had a mild fever and fatigue. What is the most likely cause?
➔ Mumps virus (Parotitis + orchitis + meningitis symptoms → Think Mumps)

Note: Transmitted via respiratory droplets
Prevented by MMR vaccine

61. A newborn has microcephaly, seizures, hepatosplenomegaly, and petechiae. CT shows periventricular calcifications. What’s the likely cause?
➔ Congenital CMV infection (periventricular calcifications is hallmark for congenital CMV infection)

Note: Differentiate form Congenital Toxoplasmosis which:
→ Causes Diffuse intracranial calcifications, Chorioretinitis,Hydrocephalus.
→ Caused by maternal infection via undercooked meat or cat feces.

62. A newborn presents with sensorineural deafness, cataracts, and a continuous machinery murmur. The mother had a low-grade fever, macular rash, and occipital lymphadenopathy during the first trimester. What is the cause?
➔ Congenital rubella syndrome (Rubella infection in early pregnancy leads to classic congenital anomalies involving the eyes, ears, and heart)

Note: Maternal clues:
→ Infection in first trimester is most dangerous
→ Presents with: Fever, maculopapular rash, postauricular/occipital lymphadenopathy

Congenital Rubella Triad: “I ♥ Earrings:
→ Sensorineural deafness (most common)
→ Cataracts
→ Cardiac defects (PDA, pulmonary stenosis)

63. A pregnant woman in Brazil develops a mild fever, rash, and conjunctivitis. Her fetus is diagnosed with microcephaly on ultrasound. What is the cause?
➔ Zika virus (Pregnant woman + mild viral illness + fetal microcephaly → Think Zika)

Note: Transmitted by Aedes mosquito
Causes congenital microcephaly and other birth defects if infection during pregnancy

64. A 10-month-old infant develops a blanching maculopapular rash on the trunk after 3 days of high fever that has now resolved. What is the cause?
➔ Human herpesvirus 6 (HHV-6) (High fever → then rash once fever resolves → classic presentation of Roseola infantum → caused by HHV-6).

Note: Differentiating Viral Exanthems

Organism	Key Features
HHV-6 (Roseola)	→ High fever (may cause seizures), followed by a diffuse macular rash that appears after fever subsides
Measles (Rubeola)	→ 4 Cs: Cough, Coryza, Conjunctivitis, Koplik spots
Coxsackie A	→ Hand, Foot, and Mouth Disease (vesicles on hands, feet, and mouth); Herpangina (posterior pharynx) → vs. Herpes ( which affects anterior oral cavity)
Rubella	→ Postauricular lymphadenopathy, pink maculopapular rash that spreads from face downward
Parvovirus B19	→ “Slapped cheek” rash + lacy reticular rash on trunk/extremities → Can cause aplastic crisis in sickle cell patients.
Streptococcus pyogenes	Scarlet fever (erythrogenic toxin), sore throat, sandpaper rash, strawberry tongue
Varicella-Zoster Virus (VZV)	Vesicular rash in multiple stages “dew drop on a rose petal” appearance

65. A 45 year old woman with chronic HCV presents with fatigue, arthralgias, and palpable purpura. Exam reveals hepatosplenomegaly and mild hypertension. What serum finding is most likely?
➔ Cryoglobulins (They are immune complexes that precipitate in cold temperatures and are strongly associated with HCV-related vasculitis)

Note: The diagnosis here is mixed Cryoglobulinemia which is associated with chronic Hepatitis C infection.
Patient with HCV presets with Arthralgias + purpura + glomerulonephritis→ think mixed Cryoglobulinemia
Key labs: Low C4 and +ve rheumatoid factor (RF)
Important clues:
→ Middle-aged woman with palpable, non-blanching rash, especially on lower limbs→ consider Cryoglobuinemia → test for HCV
→ If child with similar findings → think Henoch-Schönlein Purpura (IgA vasculitis)
Treatment: Treat underlying HCV infection

66. A 50-year-old man presents with pruritic, polygonal, purple papules on his right wrist. The lesions are flat-topped and violaceous. If this condition is triggered by a viral infection, what is characteristic of the responsible virus?
➔ Lacks 3′→5′ exonuclease proofreading activity (Symptoms suggestive of lichen planus → which is associated with Hepatitis C virus (HCV) which → lacks this proofreading ability.)

Note: Lichen planus lesion is :
→ “5 Ps” — Pruritic, Purple, Polygonal, Planar, Papules
→ Associated with chronic HCV infection → always test for HCV
HCV:
→ Is an enveloped, positive-sense, single-stranded RNA virus (Flavivirus).
→ Has no proofreading → leading to high antigenic variability → causing chronic infection.

67. A 30-year-old man is evaluated for fever and fatigue. Serology shows positive anti-HBc IgM, but negative HBsAg and anti-HBs. What is the interpretation?
➔ Window period of acute HBV infection (This is the only time where anti-HBc IgM is the sole positive marker → as HBsAg has disappeared, but anti-HBs hasn’t formed yet)

Note: Markers Summary:
HBsAg = Ongoing infection (acute or chronic)
Anti-HBs = Recovery or immunity
Anti-HBc IgM = Recent/acute infection (only marker during window)
Anti-HBc IgG = Past/chronic infection (persists for life)
HBeAg = High infectivity
Anti-HBe = Lower infectivity or recovery

Key Concepts – HBV Serology:

Phase	HBsAg	Anti-HBs	Anti-HBc	HBeAg	Anti-HBe
Incubation	+	–	–	±	–
Acute infection	+	–	+ (IgM)	+	–
Window	–	–	+ (IgM)	–	+
Recovery	–	+	+ (IgM)	–	+
Chronic infection (high infectivity)	+	–	+ (IgG)	–	–
Chronic infection (low infectivity)	+	–	+ (IgG)	–	+
Immunized	–	+	–	–	–

68. A 37 year old man develops jaundice, nausea, vomiting, and RUQ pain 2 weeks after eating raw oysters in Mexico. Exam shows scleral icterus, hepatomegaly, and loss of smoking desire. What is the pathogen?
➔ Hepatitis A virus (HAV) (Jaundice +hepatomegaly + RUQ pain (Acute viral hepatitis) + Raw shellfish (fecal-oral exposure) → think Hepatitis A virus)

Note: Anti-HAV IgM = confirms acute infection
Prevention:
→ HAV vaccine (inactivated)
→ Immune globulin for post-exposure prophylaxis
Vs Vibrio vulnificus (also found in raw oyster) but → causes sepsis or cellulitis in liver disease patients (Does NOT cause hepatitis)

69. A 1-year-old boy presents in winter with profuse watery diarrhea and signs of dehydration. He attends daycare. Stool studies are negative for leukocytes and blood.What is the cause of his symptoms?
➔ Rotavirus (watery diarrhea + daycare settings → think Rotavirus)

Note: Rotavirus is the most common cause of viral gastroenteritis in children worldwide
Prevention by Live attenuated oral vaccine:
→ given in infancy.
→ contraindicated in Severe combined immunodeficiency and if there is history of intussusception.
VS Norovirus which causes outbreaks in adults (e.g., cruise ships, nursing homes)

70. A man is bitten by a stray dog in a rural area. He has no prior vaccinations. What is the appropriate post-exposure prophylaxis?
➔ Rabies vaccine + human rabies immunoglobulin (HRIG) (Always give both vaccine and HRIG as post-exposure prophylaxis after rabies exposure in unvaccinated individuals.)

Note: Transmitted by bite from infected animals (e.g., dogs, bats, raccoons)
Histology: Negri bodies (eosinophilic cytoplasmic inclusions in neurons)
Post-exposure prophylaxis is lifesaving as rabies is nearly always fatal once symptoms appear

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Fungal

71. A 24-year-old woman on ciprofloxacin presents with 3 days of vaginal itching and discharge. No fever/cervical motion tenderness. What is the cause?
➔ Candida albicans (This is caused by antibiotic use which leads to → ↓ normal Lactobacilli → leading to Candida overgrowth)

72. A 67-year-old woman with Crohn disease develops fever (102.5°F), shaking chills, and persistent temperature spikes 7 days after central venous catheter placement. Blood cultures grow yeast forms. Which organism is responsible?
➔ Candida albicans (Catheterized or immunocompromised patients + persistent fevers + blood cultures showing yeast → think Candida)

Note: Fever persists despite antibiotics + Yeast forms seen on culture → think fungal cause
Candida albicans is the most common fungal pathogen in central line infections → especially in immunocompromised hosts
VS Top catheter-related bacterial pathogens:
→ Staph epidermidis (coagulase-negative staph) – most common bacterial cause
→ Enterococcus (gram-positive cocci) -often in ICU/abdominal surgery

73. A 40-year-old man with HIV (CD4 <50) presents with headache, fever, and confusion.Lumbar puncture shows elevated opening pressure. India ink stain reveals encapsulated yeast. What is the organism?
➔ Cryptococcus neoformans (AIDS + meningitis + India ink → Think Cryptococcus)

Note: Encapsulated yeast seen on India ink or latex agglutination (capsular antigen test)
Causes meningitis in immunocompromised (CD4 <100); ↑opening pressure on LP
Treat with Amphotericin B + flucytosine, then fluconazole (maintenance)

74. A 60-year-old man with poorly controlled diabetes presents with fever, facial pain, and black nasal discharge. Exam shows necrosis of the nasal turbinates. What is the cause?
➔ Mucor (Mucormycosis) (DKA + sinus infection + black eschar → Think Mucor)

Note: Seen in diabetics (esp. DKA) and immunocompromised patients
Non-septate, broad hyphae with right-angle branching invading blood vessels → tissue necrosis
Treat with Amphotericin B + surgical debridement

75. A 5-month-old boy presents with fever, tachypnea, and diffuse crackles. Chest X-ray shows bilateral interstitial infiltrates, and silver stain of BAL fluid shows cup-shaped cysts.
What is the diagnosis?
➔ Pneumocystis pneumonia (PCP) (Diffuse pulmonary disease + silver stain (+) BAL → think PCP)

Note: PCP (Pneumocystis jirovecii)
→ Silver stain (+) on BAL (appears as cup-shaped cysts).
→ Classic triad: Fever + hypoxemia + diffuse crackles.
→ PCP is an AIDS-defining illness.
→ Use TMP-SMX for treatment and as prophylaxis for any patient with CD4 <200 cells/mm.
Opportunistic Infections in HIV patients

CD4 Count	Opportunistic Infections	Key Features
<200	Pneumocystis jirovecii (PCP)	Subacute pneumonia, hypoxemia, silver stain (+)
<100	Toxoplasma gondii	Multiple ring-enhancing brain lesions on MRI
<100	Cytomegalovirus (CMV)	Retinitis (pizza retina), esophagitis
<50	Mycobacterium avium complex (MAC)	Fever, weight loss, hepatosplenomegaly

76. A 35-year-old HIV+ man presents with dyspnea and ground-glass opacities on CXR. Which diagnostic stain reveals the causative organism?
➔ Silver stain. (Symptoms suggestive of Pneumocystis jirovecii infection which is best visualized using silver stain)

Note: Key pathogens visualized by silver stain:
i. Pneumocystis jirovecii (PCP)
ii. Legionella pneumophila

77. A 20-year-old man in central California presents with 2 weeks of fever, dry cough, chest pain, and myalgias. Lab tests show eosinophilia, and chest X-ray reveals patchy bronchopneumonia. What is the cause?
➔ Coccidioides immitis (Southwest U.S. exposure + pneumonia + eosinophilia → Think Coccidioides)

Note: Endemic Fungi — High-Yield Comparison

Fungus	Geographic Distribution / Risk Factors	Key Features
Coccidioides immitis	Southwestern U.S (desert soil)	Spherules with endospores, bone lesions, erythema nodosum
Histoplasma capsulatum	Ohio & Mississippi River valleys, bird/bat droppings	Intracellular yeast in macrophages, granulomas
Blastomyces dermatitidis	Great Lakes	Broad-based budding yeast, skin lesions
Aspergillus spp.	Immunocompromised, old TB cavities	Septate hyphae; aspergilloma, ABPA, invasive disease
Cryptococcus neoformans	Pigeon droppings, immunocompromised	India ink positive, pulmonary nodules, meningitis

Treatment for endemic fungi is: Itraconazole (if local); Amphotericin B (if severe systemic)

78. A 42-year-old spelunker from Ohio presents with fever, cough, and fatigue. Chest X-ray shows hilar lymphadenopathy. Sputum stain shows intracellular yeast within macrophages. What is the organism?
➔ Histoplasma capsulatum (Cave exposure + Midwest + intracellular yeast in macrophages → think Histoplasmosis)

Note: Endemic to Ohio & Mississippi River valleys
Exposure: Bird/bat droppings (e.g., caves)
Found inside macrophages → granulomatous inflammation

79. A 52-year-old construction worker from Indiana presents with chronic fever, dry cough, and bilateral interstitial infiltrates. Transbronchial biopsy reveals fungal elements.
What cell wall component is most characteristic of the causative organism?
➔ Glucans (Fungal infections has Glucans in cell wall (vs. peptidoglycan in bacteria)

HY Cell Wall Components Summary:

Component	Organism Type
Glucans	Fungi
Peptidoglycan + Teichoic acid	Gram-positive bacteria
Peptidoglycan + LPS	Gram-negative bacteria (LPS = endotoxin)
Polypeptide capsule (poly-D-glutamate)	Bacillus anthracis (unique capsule)
Cord factor	Mycobacterium tuberculosis

80. A 55-year-old man presents with a 7-year history of red, scaly plaques on his back/buttocks, unresponsive to emollients and topical steroids. He has eosinophilia and elevated IgA/IgE. What is the cell type causing these findings?
➔ T lymphocytes (mycosis fungoides) (It is a cutaneous T-cell lymphoma that is suspected when you see chronic scaly rashes unresponsive to treatment with eosinophilia and high IgE/IgA.)

Note: Mimics tinea but fails to improve with steroids/antifungals
Labs: Eosinophilia + high IgE/IgA → from cytokines (e.g., IL-5) secreted by malignant T-cells
Biopsy: Pautrier microabscesses = malignant CD4+ T-cells in epidermis

81. A 30-year-old wrestler presents with an itchy, circular, red rash with a central clearing on his forearm. KOH prep of skin scrapings shows segmented hyphae. What is the most likely diagnosis?
➔ Tinea corporis (Ringworm: annular rash + central clearing + contact sports → Dermatophyte infection)

Note: Key feature: Annular scaly plaque with central clearing
Risk: Contact sports (e.g., wrestling), shared surfaces
Diagnosis: KOH prep → septate hyphae
Treatment: Topical antifungals (e.g., terbinafine); oral if extensive

82. A 27-year-old man presents with worsening hypopigmented skin patches for 2 years. No other abnormalities are noted. What is the most likely cause?
➔ Malassezia furfur (tinea versicolor) (Scaly hypopigmented or hyperpigmented patches on the trunk → Think tinea versicolor → confirm with KOH prep.)

Note: High-Yield Differentials: Hypopigmented Skin Lesions

Condition	Key Features	Diagnosis
Tinea Versicolor	– Hypo/hyperpigmented scaly patches (chest/back) – Worse in warm, humid climates	– KOH prep: “Spaghetti & meatballs” (hyphae + yeast)
Vitiligo	– Sharply demarcated milky-white patches (non-scaly) – Associated with autoimmune diseases	– Clinical – Wood’s lamp accentuates depigmentation
Pityriasis Alba	– Ill-defined, hypopigmented patches (especially children’s face/arms) – Mild scaling, post-inflammatory	– Clinical

83. A 45-year-old gardener presents with a painless ulcer on his hand that developed after a rose thorn injury. Over the next week, several nodules appeared along the path of lymphatic drainage. What is the organism?
➔ Sporothrix schenckii (Rose thorn + nodular lymphangitis → Think Sporotrichosis)

Note: Causes subcutaneous ulcers with nodular spread along lymphatics

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Parasites

84. A 20-year-old lifeguard from Long Island, NY presents with fever, chills, and headache after tick exposure. Malaria PCR is negative. What is the cause?
➔ Babesia microti (babesiosis) (Tick-borne protozoan infection endemic to the Northeastern U.S. causing malaria-like symptoms.)

Note: Key Diagnostic Clues:
→ Location: Northeast USA (e.g., Long Island)
→ Vector: Ixodes scapularis (same tick as Lyme & Anaplasma)
→ Lab: Intraerythrocytic parasites (± Maltese cross) on Giemsa stain + negative Malaria smear/PCR
If the patient is from the Northeastern U.S. with flu-like symptoms after a tick bite → think of Babesiosis or Lyme disease VS if from the Middle East or Southeast Asia →think Malaria.

85. A 30-year-old man presents with cyclic fever (102°F), chills, and headache after traveling to southern Mexico. Wright-stained blood smear shows intraerythrocytic parasites. Which vector transmitted this infection?
➔ Anopheles Mosquito (Cyclic symptoms + travelling to endemic regions → think Plasmodium malaria → transmitted by Anopheles species)

Note: Malaria Endemic regions are Mexico (rural areas), Africa, SE Asia.
Diagnosis: Wright/Giemsa stain shows intraerythrocytic parasites (ring forms, schizonts).
Treatment:
→ Uncomplicated malaria: Chloroquine (if sensitive) or artemisinin-based therapy.
→ Severe malaria: IV artesunate.
→ Primaquine: Eliminates dormant liver hypnozoites in P. vivax & P. ovale → Prevents relapse → Always test G6PD before giving primaquine (risk of hemolysis!).

Species-Specific Fever Patterns:

Organism	Fever pattern
P.vivax & ovale	Fever every 48 Hrs (3rd day)
P.malariae	Fever every 72 Hrs (4th day)
P.falciparum	irregular fever pattern + can occlude vessels including cerebral vessels
Babesia	Irregular fever + risk ↑ in asplenic patients

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86. A 30-year-old HIV+ man presents with watery diarrhea, weight loss, and cramping for 10 days. Stool microscopy confirms the diagnosis. What is the cause?
➔ Cryptosporidium (HIV + profuse watery Diarrhea → think Cryptosporidium)

Note: Stool microscopy shows acid-fast oocysts with no blood/WBCs

Differential Diagnosis of Diarrhea in HIV+ Patients:

Organism	Key Features
Cryptosporidium	Watery diarrhea, acid-fast oocysts, no blood/WBCs
CMV	Bloody diarrhea + abdominal pain + ulcers (colon biopsy)
Mycobacterium avium	Watery diarrhea + fever + weight loss + ↑ ALP

87. A 27-year-old marine stationed in Saudi Arabia presents with fever, fatigue, malaise, anemia, and lymphadenopathy 2 weeks after a sand fly bite. Skin biopsy shows macrophages filled with intracellular organisms. What is the cause?
➔ Leishmania tropica (Travel to the Middle East + sand fly bite → think Leishmania)

Note: Biopsy: shows Intracellular amastigotes in macrophages.

88. A 6-year-old boy presents with severe nocturnal itching and a rash in skin folds. Which skin finding is pathognomonic for this condition?
➔ Burrows (serpiginous gray-white tracks in web spaces/wrists that is suggestive for scabies infection)

Note: Nocturnal pruritus: Worsens at night due to increased mite activity.
All close contacts should be treated simultaneously.

89. A 3-year-old boy from India presents with abdominal distention, vomiting, and visible 20-cm worms in stool. Bowel sounds are high-pitched. What is the cause?
➔ Ascaris lumbricoides (Symptoms suggestive of intestinal obstruction due to worm burden)

Note: High-Yield Summary: Intestinal Nematodes

Organism	Classic Presentation	Diagnosis
Enterobius vermicularis (Pinworm)	Child with perianal/perivulvar itching	Scotch tape test (eggs on tape)
Ascaris lumbricoides (Roundworm)	Abdominal pain, intestinal obstruction	Stool microscopy (ova detection)
Strongyloides stercoralis	Lung symptoms (hemoptysis, dyspnea), GI symptoms (especially in immunocompromised)	Rhabditiform larvae in stool
Ancylostoma duodenale & Necator americanus (Hookworm)	Iron deficiency anemia	Stool microscopy (hookworm eggs)
Trichinella spiralis	Muscle pain, cysts in striated muscles	Muscle biopsy, Serology

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90. A 35-year-old woman with fatigue, pallor, and anemia (Hb 7.2 g/dL) after travel to Brazil and animal exposure. What is the most likely cause?
➔ Necator americanus (hookworm) (Iron-deficiency anemia + travel to endemic area + skin exposure (barefoot) → think hookworm infection.)

Note: Hookworms (Necator americanus & Ancylostoma duodenale):
→ Transmitted by Barefoot contact with contaminated soil (larvae penetrate skin).
→ Causes Iron-deficiency anemia
→ Treatment: Albendazole
VS Diphyllobothrium latum (Fish Tapeworm) which causes Vitamin B12 deficiency leading to megaloblastic anemia (high MCV)
→transmitted by Raw/undercooked freshwater fish.

91. A 34-year-old man who recently traveled to Mexico presents with fever, right upper quadrant pain, and bloody diarrhea. Liver ultrasound shows a solitary hypoechoic lesion.. What is the organism?
➔ Entamoeba histolytica (Travel + bloody diarrhea + liver abscess + trophozoites with RBCs → Think Entamoeba)

Note: Causes bloody diarrhea with flask-shaped ulcers in colon + liver abscess (“anchovy paste” aspirate)
Treat with metronidazole (for tissue invasion) + paromomycin (to eliminate luminal cysts)

92. A 40-year-old man from rural Bolivia presents with worsening shortness of breath and palpitations. He also reports long-standing difficulty swallowing solids.. What is the cause?
➔ Trypanosoma cruzi (Immigrant + heart failure + achalasia/constipation → Think Chagas)

Note: Causes Chagas disease → dilated cardiomyopathy, achalasia (megaesophagus), megacolon
Transmitted by kissing bug
Diagnosed by Trypomastigotes in blood

93. A Middle Eastern farmer presents with right upper quadrant pain. Liver imaging shows a fluid-filled cyst with internal daughter cysts. During surgery, he develops sudden hypotension. What is the cause?
➔ Echinococcus granulosus (Liver cyst + exposure to sheep/dogs + anaphylaxis on rupture → think Echinococcus)

Note: Cyst rupture → leads to anaphylaxis due to antigen release

94. A 12-year-old girl from Mexico presents with new-onset seizures. Head CT reveals multiple calcified nodules and cystic lesions. What is the diagnosis?
➔ Neurocysticercosis (Patient from an endemic region +seizures and brain cysts + calcifications → suspect neurocysticercosis)

Note: High-Yield Differentials: Seizures + Brain Lesions

Condition	Key Features	Common in
Neurocysticercosis (Taenia solium)	Multiple cysts and calcifications, seizures,	Endemic areas
Toxoplasmosis (T. gondii)	Ring-enhancing lesions on MRI/CT, no calcifications	HIV/AIDS, CD4 <100
Primary CNS Lymphoma	Single or few periventricular enhancing masses, B symptoms	HIV/AIDS, EBV+

95. A 26-year-old swimmer from Egypt presents with hematuria and dysuria. Urine microscopy shows an ova with a terminal spine. What is the causative organism?
➔ Schistosoma haematobium(Terminal spine + hematuria + freshwater exposure in endemic region → think S. haematobium)

Note: Schistosomiasis is contracted via skin penetration in freshwater containing cercariae from snails.

Schistosoma Species & Egg Spine

Species	Location Affected	Egg Spine	Key Clue
S. haematobium	Bladder (urinary tract)	Terminal spine	Hematuria, squamous cell CA
S. mansoni	Intestine/liver	Lateral spine	Portal HTN

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Pharmacology

96. An 18-year-old man presents with a painless penile ulcer followed weeks later by a maculopapular rash involving the palms and soles. What microbial process is inhibited by the drug of choice?
➔ Cell wall synthesis (Symptoms suggestive of Syphilis → treated with Penicillin G → which inhibits bacterial transpeptidases → blocking peptidoglycan cross-linking)

Note: Syphilis:
→ Penicillin G is the drug of choice for all stages
→ The patient can develop flu-like symptoms post-treatment → this called Jarisch-Herxheimer reaction → occurs due to endotoxin-like release from dying spirochetes
Penicillin resistance is generally → Caused by
→ β-lactamase production (breaks down the drug)
→ altered penicillin-binding proteins (PBPs) (lowers drug binding affinity)

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97. A 23-year-old military recruit has fever, cough, fatigue, and bilateral CXR infiltrates. Which medication is ineffective?
➔ β-lactams (atypical pneumonia + young adults especially military recruits and students → think Mycoplasma pneumoniae → which lacks cell wall → making β-lactams ineffective)

Note: A gradual onset of symptoms with diffuse + bilateral infiltrates → think atypical pneumonia.
Causes cold agglutinin formation (IgM autoantibodies against RBCs) → can cause hemolytic anemia

98. A 62-year-old man develops fever, hypotension, and red flushing over the face, neck, and upper torso after receiving IV antibiotics for MRSA bacteremia. Which bacterial process is inhibited by this antibiotic?
➔ Cell wall synthesis (Symptoms indicate Red Man Syndrome, a known adverse effect of vancomycin)

Note: Mechanism: Binds D-Ala-D-Ala → prevents transglycosylation → inhibits cell wall synthesis
Covers: MRSA, C. difficile (oral), resistant Gram-positives
Key Side Effects:
→ Red Man Syndrome (due to histamine release) → not IgE-mediated
→ Nephrotoxicity
→ Ototoxicity

99. A healthy term newborn receives prophylactic antibiotic eye ointment shortly after vaginal delivery. Which bacterial process does this treatment inhibit?
➔ Bacterial protein synthesis (Erythromycin inhibits the 50S ribosomal subunit → preventing protein synthesis in bacteria like Neisseria gonorrhoeae)

Note: Purpose of Prophylaxis is to prevent neonatal ophthalmia from:
→ Neisseria gonorrhoeae
→ Chlamydia trachomatis

100. A 48-year-old renal transplant recipient on chronic steroids presents with high-grade fever (104°F), nonproductive cough, and right lower lobe infiltrate on imaging. He is diagnosed with Legionella pneumonia. What is the mechanism of the most appropriate antibiotic?
➔ Inhibits DNA gyrase (topoisomerase II) (Fluoroquinolones are used for Legionella and acts by inhibiting DNA gyrase to block bacterial DNA replication)

Note: Fluoroquinolones Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → halting bacterial DNA replication.

101. 45-year-old long-distance runner with recent antibiotic use presents with Achilles tendon rupture. Which drug most likely caused this?
➔ Levofloxacin (Fluoroquinolones like levofloxacin impair collagen synthesis and increase the risk of tendon rupture)

Note: Risk factors for tendon rupture are Age >60, Concurrent corticosteroid use and Athletes or high mechanical stress (e.g., runners)
Other Notable Adverse Effects include → QT prolongation → avoid in patients with cardiac conditions

102. A 24-year-old woman presents with a dental abscess and swelling of the jaw. She is allergic to penicillin. Which of the following is the most appropriate antibiotic to treat this anaerobic infection?
➔ Clindamycin (Effective against anaerobic infections above the diaphragm, especially in penicillin-allergic patients)

Note: Inhibits 50S ribosomal subunit → blocks translocation
Major risk for causing C. difficile colitis

103. An 85-year-old hospitalized man is treated for Pseudomonas aeruginosa pneumonia. Two days later, his creatinine rises from 0.8 mg/dL to 2.0 mg/dL. Which of the following antibiotics is the cause of his acute kidney injury?
➔ Gentamicin (An aminoglycoside known for nephrotoxicity, especially in elderly patients)

Note: Aminoglycoside toxicity triad:
→ Nephrotoxicity → acute tubular necrosis (most common)
→ Ototoxicity (↑ risk with loop diuretics)
→ Neuromuscular blockade
Risk factors for adverse effects: Elderly age, pre-existing renal disease, concurrent nephrotoxic agents (loop diuretics)

104. An 18-year-old college student presents with 7 days of low-grade fever, nonproductive cough, and fatigue. Physical examination is unremarkable. Chest X-ray reveals bilateral interstitial infiltrates. What is the most appropriate treatment?
➔ Azithromycin (Atypical pneumonia + in young student→ think Mycoplasma pneumoniae → macrolides as azithromycin are first line)

Note: Azithromycin is a macrolide antibiotic that inhibits the 50S ribosomal subunit, blocking protein synthesis.

105. A 28-year-old hiker presents with fever, headache, and a petechial rash that began on the wrists and ankles. He recently returned from a camping trip in North Carolina. Which is the most appropriate treatment?
➔ Doxycycline (Tetracycline class) (Used to treat Rocky Mountain spotted fever, a tick-borne illness caused by Rickettsia rickettsii)

Note: Binds 30S ribosomal subunit → inhibits protein synthesis
Used for tick-borne illnesses (Rickettsia, Lyme) & atypical pneumonia
Side effects: photosensitivity, teeth staining in kids, avoid in pregnancy

106. A 17-year-old boy is treated with doxycycline for acne but sees no improvement after taking it regularly with milk. What is the most likely explanation?
➔ Chelation with calcium (Tetracyclines bind calcium in milk → forming non-absorbable complexes that reduce drug efficacy)

Note: Tetracyclines bind divalent cations (Ca²⁺, Mg²⁺, Fe²⁺, Al³⁺) → forming non-absorbable complexes that reduce drug efficacy
Avoid with dairy/antacids (binds divalent cations → ↓ absorption)

107. A 34-year-old man with HIV presents with fever, non-productive cough, and dyspnea. Chest X-ray shows bilateral ground-glass opacities. CD4 count is 150/mm³. Which of the following is the most appropriate treatment?
➔ TMP-SMX (Trimethoprim-Sulfamethoxazole) (Used to treat and prevent Pneumocystis jirovecii pneumonia in immunocompromised patients)

Note: Blocks folate synthesis at two steps
Also treats Nocardia, UTIs, and Toxoplasma prophylaxis (CD4 < 100)
Side effects: Megaloblastic anemia, hyperkalemia, rash, G6PD hemolysis

TMP-SMX mechanism of action

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108. A 35-year-old man diagnosed with pulmonary tuberculosis is started on combination therapy including Rifampin. Which bacterial process is inhibited by Rifampin?
➔ DNA-dependent RNA polymerase (Rifampin inhibits bacterial RNA polymerase → blocking transcription)

Note: Rifampin is a key drug in TB treatment as part of the RIPE regimen:
○ Rifampin
○ Isoniazid
○ Pyrazinamide
○ Ethambutol
Causes orange-red discoloration of body fluids
Strong CYP450 inducer → reduces effectiveness of many drugs (e.g., oral contraceptives, warfarin)

109. A 50-year-old man with a history of tuberculosis presents with fatigue and a burning sensation in his hands. What is the most appropriate treatment?
➔ Vitamin B6 (Patient with TB is most likely taking isoniazid which depletes pyridoxine(B6), leading to peripheral neuropathy, which is prevented by B6 supplementation)

Note: Vitamin B6 should be co-administered with isoniazid to prevent neuropathy.

110. A 20-year-old woman on antibiotics presents with vulvar itching and thick white vaginal discharge. Vaginal pH is 4.2. What is the mechanism of the most appropriate oral treatment?
➔ Inhibits fungal CYP450 (Symptoms suggestive of candidiasis treated with Fluconazole which → Inhibits fungal CYP450 → leading to ergosterol synthesis inhibition)

Note: Risk factors for candidiasis are antibiotic use, diabetes, immunosuppression and OCPs.
Fluconazole is the drug of choice for uncomplicated vulvovaginal candidiasis

111. A 25-year-old patient on a stable dose of warfarin develops bleeding after recent treatment for candida esophagitis with fluconazole. What is the mechanism?
➔ Cytochrome P450 enzymes inhibition (Warfarin is metabolized by cytochrome P450 so → CYP450 inhibitors like fluconazole → ↑ bleeding risk by raising drug levels)

Note: CYP450 inhibitors → enhance drug effects VS CYP450 inhibitors inducers → reduce drug effects.
CYP450 inhibitors Mnemonic – COKE + PIe + Grapefruit:
→ Cimetidine/Ciprofloxacin,
→ Omeprazole,
→ Ketoconazole,
→ Erythromycin,
→ Protease Inhibitors,
→ Grapefruit juice

112. An 18-year-old neutropenic (ANC <500/mm³) leukemia patient presents with fever, pleuritic chest pain, and left lung infiltrate with effusion. BAL fluid shows PAS-positive organisms. What is the most appropriate treatment?
➔ Amphotericin B (Symptoms in an immunocompromised host with PAS-positive organisms suggest → invasive aspergillosis → treated with Amphotericin B)

Note: Amphotericin B → binds ergosterol in fungal membranes → forms pores → causing cell death

113. A 22-year-old man presents with chronic foul-smelling diarrhea and weight loss after traveling to Indonesia. Stool microscopy reveals protozoa. What is the drug’s mechanism of action for this infection?
➔ Forms free radicals (Symptoms suggestive of Giardia → treated with Metronidazole which forms free radicals that damage protozoal DNA)

Note: Metronidazole is used in the treatment of Giardia, Entameba, Trichomonas, Gardenerella (“GET in the Metro, Gee!”)
Key side effect of Metronidazole is Disulfiram-like reaction — classically seen as flushing, GI upset, and tachycardia after alcohol use during treatment for Trichomonas vaginal infections.

114. Drug X treats trematode/cestode infections by increasing calcium influx into parasites, causing paralysis and death. Which drug does this describe?
➔ Praziquantel (It disrupts calcium homeostasis → leading to paralysis and death of the parasite)

Note: Covers:
→ Trematodes (e.g., Schistosoma spp.)
→ Cestodes (e.g., Taenia solium, Diphyllobothrium latum)
Does not cover Nematodes (roundworms) → Use Albendazole or Mebendazole

115. A 39-year-old woman on chemotherapy for AML develops painful lip vesicles progressing to clear fluid-filled lesions. What drug mechanism is most appropriate for treatment?
➔ DNA polymerase inhibitor (Symptoms are suggestive of HSV reactivation → which is treated with antivirals that inhibit viral DNA polymerase (Acyclovir).)

Note: Herpes Simplex Virus (HSV) Reactivation:
→ Triggers: Immunosuppression (chemotherapy, HIV).
→ Presentation: Pain/tingling (prodrome) → clustered vesicles on lips/genitals.
→ Treatment: Acyclovir, valacyclovir, famciclovir — inhibit viral DNA polymerase

116. A 25-year-old man presents with penile vesicles/ulcers resolving in 1 week. Which viral enzyme is required to activate first-line treatment?
➔ Thymidine kinase (HSV uses its own thymidine kinase to phosphorylate and activate acyclovir/valacyclovir)

Note: HSV treatment:
→ Acyclovir or valacyclovir (guanosine analogs) (1st-line)
→ Mechanism: Viral thymidine kinase phosphorylates the drug → Active triphosphate form inhibits viral DNA polymerase → leads to chain termination
Acyclovir can cause nephrotoxicity (crystal-induced) → so adequate hydration is required during IV infusion of the medication.
Resistance is caused by mutated or absent viral thymidine kinase → Use foscarnet (direct DNA polymerase inhibitor → needs no activation)
CMV Lacks thymidine kinase → use ganciclovir or foscarnet

117. A 22-year-old HIV-positive woman on ritonavir and lopinavir develops drug resistance. Mutation in which viral enzyme is most likely responsible?
➔ HIV protease (Protease inhibitors block viral protein processing → Mutations in HIV protease prevent effective drug binding → leading to resistance)

Note: Key side effects include; hyperglycemia, hyperlipidemia and Lipodystrophy (fat redistribution)
Rapid Clues: HIV Drug Classes & Their Adverse Effects:

Adverse effect	Think
Metabolic syndrome	Protease inhibitors “ritonavir, lopinavir”
Myopathy (↑ CK)	Integrase inhibitors “raltgravir”
Rash	NNRTIs “nevirapine”
Nephropathy + BM suppression	NRTIs “Abacavir, Zidovudine”

118. A 32-year-old man with advanced HIV (CD4 count: 55/mm³) presents with broad resistance to protease inhibitors, NNRTIs and NRTIs. Which antiretroviral agent is most likely to remain effective?
➔ Enfuvirtide (It is a fusion inhibitor that acts on gp41 and is unaffected by resistance to reverse transcriptase or protease inhibitors)

Note: It is used in patients with multi-drug resistant HIV.

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Version 1.0 May 2025. No part of this document may be reproduced or distributed without written permission. For personal study only. Medical information herein is for educational purposes and does not constitute clinical advice. Always confirm with current guidelines and your institution’s policies.

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USMLE Step 1 High‐Yield Microbiology Topics

Microbiology

High Yield USMLE Step 1 Notes

Table of Contents

Bacteria

VIRAL

Fungal

Parasites

Pharmacology

🏁 Final Thoughts

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