MCCQE Antimicrobial Pharmacology 3 — Questions and Answers
Question 1: A patient with HIV and a CD4 count of 50 cells/µL develops Pneumocystis jirovecii pneumonia. First-line treatment is trimethoprim-sulfamethoxazole (TMP-SMX). Which electrolyte abnormality must be closely monitored?
- Hyponatremia from SIADH
- Hyperkalemia due to trimethoprim's amiloride-like effect on the collecting duct (Correct answer)
- Hypocalcemia from calcium chelation
- Hypomagnesemia from renal wasting
Correct answer: Hyperkalemia due to trimethoprim's amiloride-like effect on the collecting duct
Trimethoprim blocks epithelial sodium channels in the distal nephron similar to amiloride, reducing potassium excretion and causing hyperkalemia.
Question 2: Which class of antibiotics acts by inhibiting bacterial cell wall synthesis through binding penicillin-binding proteins (PBPs) and is naturally resistant to beta-lactamases?
- Carbapenems (Correct answer)
- Monobactams
- Glycopeptides
- Polymyxins
Correct answer: Carbapenems
Carbapenems bind PBPs to inhibit cell wall synthesis and have inherent stability against most beta-lactamases due to their unique bicyclic ring structure.
Question 3: Fluconazole is effective against Candida albicans but often ineffective against Candida krusei. Which mechanism explains this intrinsic resistance?
- C. krusei produces beta-glucan that prevents fluconazole entry
- C. krusei has an intrinsically less susceptible CYP51 target enzyme (Correct answer)
- C. krusei overexpresses efflux pumps constitutively
- C. krusei produces a fluconazole-inactivating acetylase
Correct answer: C. krusei has an intrinsically less susceptible CYP51 target enzyme
Candida krusei has intrinsic resistance to fluconazole primarily due to reduced affinity of its lanosterol 14α-demethylase (CYP51) target for the drug.
Question 4: A 65-year-old patient on fluoroquinolone therapy develops sudden Achilles tendon rupture. Which mechanism underlies this adverse effect?
- Fluoroquinolones chelate magnesium in collagen-producing cells, disrupting matrix metalloprotease regulation (Correct answer)
- They inhibit topoisomerase IV in human tenocytes, causing mitotic arrest
- They deplete mitochondrial DNA in tendons, causing energy failure
- They competitively block glycine incorporation into collagen fibrils
Correct answer: Fluoroquinolones chelate magnesium in collagen-producing cells, disrupting matrix metalloprotease regulation
Fluoroquinolones chelate divalent cations like magnesium in tenocytes, disrupting matrix metalloprotease homeostasis and degrading collagen in tendons.
Question 5: Which antifungal drug works by inhibiting 1,3-beta-D-glucan synthase, disrupting the fungal cell wall?
- Amphotericin B
- Voriconazole
- Caspofungin (Correct answer)
- Flucytosine
Correct answer: Caspofungin
Caspofungin is an echinocandin that inhibits 1,3-beta-D-glucan synthase, reducing glucan polymer synthesis in the fungal cell wall.
Question 6: A patient with Clostridium difficile infection fails metronidazole therapy. What is the most appropriate next step?
- Switch to intravenous metronidazole at higher doses
- Start oral vancomycin (Correct answer)
- Add rifaximin to current metronidazole
- Initiate intravenous vancomycin
Correct answer: Start oral vancomycin
Oral vancomycin is recommended for patients who fail or are intolerant to metronidazole for C. difficile infection, as it achieves high luminal concentrations.
Question 7: Which antibiotic requires dose adjustment in patients with renal failure but NOT in patients with hepatic failure?
- Metronidazole
- Azithromycin
- Gentamicin (Correct answer)
- Clindamycin
Correct answer: Gentamicin
Gentamicin is almost entirely renally excreted without hepatic metabolism, requiring dose reduction in renal failure but not in hepatic impairment.
MCCQE Antimicrobial Pharmacology 3
A patient with HIV and a CD4 count of 50 cells/µL develops Pneumocystis jirovecii pneumonia.
First-line treatment is trimethoprim-sulfamethoxazole (TMP-SMX).
Which electrolyte abnormality must be closely monitored?