MCCQE Antimicrobial Pharmacology 2 — Questions and Answers
Question 1: A patient with a penicillin allergy requires treatment for a serious Staphylococcus aureus infection. Which antibiotic has the highest risk of cross-reactivity with penicillin?
- Aztreonam
- Cefazolin (Correct answer)
- Imipenem
- Vancomycin
Correct answer: Cefazolin
First-generation cephalosporins like cefazolin share a similar R1 side chain with some penicillins, conferring the highest cross-reactivity risk among beta-lactams.
Question 2: Which mechanism best explains why aminoglycosides exhibit concentration-dependent bactericidal activity?
- They irreversibly bind the 50S ribosomal subunit at higher concentrations
- Higher peak concentrations drive greater uptake into bacteria via the electron transport chain (Correct answer)
- They inhibit DNA gyrase more potently at elevated concentrations
- They competitively inhibit transpeptidase in a concentration-dependent manner
Correct answer: Higher peak concentrations drive greater uptake into bacteria via the electron transport chain
Aminoglycoside uptake into bacterial cells is energy-dependent and increases with higher drug concentrations, producing a concentration-dependent kill curve.
Question 3: A patient on warfarin develops a urinary tract infection. Which antibiotic choice requires the most careful INR monitoring due to interaction with warfarin metabolism?
- Nitrofurantoin
- Trimethoprim-sulfamethoxazole (Correct answer)
- Fosfomycin
- Pivmecillinam
Correct answer: Trimethoprim-sulfamethoxazole
Trimethoprim-sulfamethoxazole inhibits CYP2C9, reducing warfarin metabolism and significantly elevating INR, increasing hemorrhage risk.
Question 4: Daptomycin is contraindicated for the treatment of Staphylococcus aureus pneumonia because:
- It is inactivated by pulmonary surfactant (Correct answer)
- It does not penetrate the blood-brain barrier
- It is exclusively excreted by the kidneys and causes nephrotoxicity
- It induces beta-lactamase production in S. aureus
Correct answer: It is inactivated by pulmonary surfactant
Pulmonary surfactant binds and inactivates daptomycin, rendering it ineffective for lung infections.
Question 5: Which pharmacokinetic property makes once-daily dosing of aminoglycosides advantageous compared to traditional thrice-daily dosing?
- Improved time-dependent killing reduces total dose needed
- The post-antibiotic effect allows bacterial suppression between doses (Correct answer)
- Renal tubular saturation during the trough period reduces nephrotoxicity
- Extended half-life with once-daily dosing avoids peak toxicity
Correct answer: The post-antibiotic effect allows bacterial suppression between doses
Aminoglycosides exhibit a prolonged post-antibiotic effect (PAE), meaning bacterial growth remains suppressed even after drug levels fall below the MIC.
Question 6: A patient receiving prolonged vancomycin therapy develops sensorineural hearing loss. This toxicity is most likely related to which pharmacokinetic parameter?
- Excessively low trough levels
- Elevated vancomycin AUC/MIC ratio
- Concurrent use of loop diuretics increasing peak levels
- Renal insufficiency causing drug accumulation and high troughs (Correct answer)
Correct answer: Renal insufficiency causing drug accumulation and high troughs
Ototoxicity from vancomycin is most strongly associated with drug accumulation due to renal impairment, leading to persistently elevated trough concentrations.
Question 7: Which statement accurately describes the mechanism of action of linezolid?
- It inhibits the 30S ribosomal subunit, preventing tRNA binding
- It binds the 50S subunit at the peptidyl transferase center, preventing initiation complex formation (Correct answer)
- It inhibits bacterial DNA gyrase and topoisomerase IV
- It disrupts the cytoplasmic membrane via calcium-dependent depolarization
Correct answer: It binds the 50S subunit at the peptidyl transferase center, preventing initiation complex formation
Linezolid binds the 23S rRNA of the 50S subunit, blocking formation of the 70S initiation complex and halting protein synthesis.
MCCQE Antimicrobial Pharmacology 2
A patient with a penicillin allergy requires treatment for a serious Staphylococcus aureus infection.
Which antibiotic has the highest risk of cross-reactivity with penicillin?