Obscure Mechanisms, Rare Toxicities, Complex PK/PD, Multidrug Resistance, and Challenging
Clinical Conundrums.
Instructions
Select all that apply for each question. Correct answers are bolded. Explanations are provided for each
choice. This set is intentionally difficult.
Questions 1–150
1. Which statements about the mechanism of vancomycin resistance in Enterococcus faecium (VanA
phenotype) are correct?
A) Alters the terminal D-Ala-D-Ala to D-Ala-D-Lac – *Correct; reduces vancomycin binding affinity
1000-fold.*
B) VanA gene cluster is plasmid-mediated – Correct; transferable to MRSA (VRSA).
C) Resistant to both vancomycin and teicoplanin – Correct; distinguishes VanA from VanB.
D) Induced by glycopeptide exposure – Correct; expression regulated by two-component system.
E) Only occurs in E. faecalis – *Incorrect; more common in E. faecium.
✅ Correct: A, B, C, D
2. Which mechanisms contribute to Pseudomonas aeruginosa resistance to carbapenems?
A) Loss of OprD porin (imipenem specific) – Correct; prevents imipenem entry.
B) Upregulated efflux pumps (MexAB-OprM) – Correct; meropenem efflux.
C) Carbapenemase production (KPC, VIM, NDM) – Correct; hydrolyzes carbapenems.
D) Modification of penicillin-binding proteins – Correct; reduced affinity.
E) Biofilm formation – Correct; physical barrier and reduced penetration.
✅ Correct: A, B, C, D, E
3. Which statements about the pharmacokinetics of ceftriaxone are correct?
A) 90% renally excreted – *Incorrect; 40-50% renal, 50-60% biliary.*
B) Biliary excretion can cause pseudolithiasis – Correct; calcium-ceftriaxone precipitate in
gallbladder.
C) No dose adjustment in renal failure – Correct; safe even in ESRD.
, D) High protein binding (85-95%) – Correct; displaces bilirubin in neonates.
E) Once-daily dosing due to long half-life (6-9 hours) – Correct; prolonged beta-lactam.
✅ Correct: B, C, D, E
4. A patient with Candida glabrata fungemia fails fluconazole. The isolate is resistant to echinocandins
(FKS mutant). Which options remain?
A) Amphotericin B lipid complex – Correct; no cross-resistance.
B) High-dose fluconazole (800-1200 mg/day) – Incorrect; FKS mutation does not affect fluconazole
but C. glabrata is often fluconazole-resistant anyway.
C) Voriconazole – Variable; cross-resistance with fluconazole common.
D) Flucytosine (combination with amphotericin B) – Correct; synergistic.
E) Ibrexafungerp (oral glucan synthase inhibitor) – Correct; novel class, active against FKS mutants.
✅ Correct: A, D, E
5. Which statements about the mechanism of linezolid resistance are correct?
A) Mutation in 23S rRNA (G2576T) – Correct; most common in enterococci and staphylococci.
B) cfr (chloramphenicol-florfenicol resistance) methyltransferase – Correct; plasmid-mediated; also
confers resistance to florfenicol, clindamycin.
C) optrA gene (ABC transporter) – Correct; efflux of oxazolidinones and phenicols.
D) Resistance develops rapidly during monotherapy – Correct; especially with prolonged use.
E) Linezolid resistance is always high-level (MIC >8) – *Incorrect; can be low-level (MIC 4-8).*
✅ Correct: A, B, C, D
6. A patient with MRSA bacteremia on vancomycin has a vancomycin MIC of 2 mcg/mL by broth
microdilution. Which statements are correct?
A) Vancomycin is still effective if AUC/MIC ≥400 – Correct; but achieving AUC 800 is difficult.
B) Alternative therapy (daptomycin or ceftaroline) should be considered – Correct; MIC ≥2 is
associated with treatment failure.
C) Add gentamicin for synergy – Incorrect; nephrotoxic, no proven benefit.
D) Add rifampin – Incorrect; no benefit in bacteremia, increases resistance.
E) Check for vancomycin heteroresistance – Correct; subpopulations with higher MIC.
✅ Correct: A, B, E
7. Which statements about the post-antibiotic effect (PAE) are correct?
A) Longer with concentration-dependent killers (aminoglycosides) – Correct; hours of suppression
after levels fall.
B) Short or absent with beta-lactams against gram-negatives – Correct; regrowth quickly.
, C) Prolonged by sub-MIC antibiotic levels – Correct; low levels extend PAE.
D) PAE allows extended-interval dosing – Correct; once-daily aminoglycosides.
E) Biofilm organisms have prolonged PAE – Incorrect; biofilms reduce PAE.
✅ Correct: A, B, C, D
8. Which statements about the "inoculum effect" are correct?
A) Higher bacterial density increases MIC – Correct; especially beta-lactams against S. aureus.
B) Beta-lactamase-producing organisms show marked inoculum effect – Correct; more enzyme
overwhelms drug.
C) Clindamycin shows inoculum effect – Correct; bacteriostatic drugs less affected.
D) Daptomycin shows no inoculum effect – Correct; concentration-dependent.
E) Inoculum effect explains failure in high-burden infections (endocarditis, abscess) – Correct.
✅ Correct: A, B, D, E
9. Which statements about the Eagle effect (paradoxical growth at high antibiotic concentrations) are
correct?
A) Observed with penicillin against enterococci – Correct; very high doses less effective.
B) Mechanism may involve autolysin inhibition – Correct; high penicillin suppresses autolysins.
C) Relevant in enterococcal endocarditis – Correct; avoid extremely high penicillin doses.
D) Also seen with aminoglycosides – Correct; high concentrations may suppress killing.
E) Clinically significant for all beta-lactams – Incorrect; rare and organism-specific.
✅ Correct: A, B, C, D
10. Which statements about the "see-saw effect" in MRSA are correct?
A) Beta-lactam susceptibility increases when vancomycin resistance increases – Correct; VISA
strains often become beta-lactam susceptible.
B) Mechanism involves cell wall thickening and PBP2a expression changes – Correct.
C) Ceftaroline may retain activity against VISA – Correct; used in combination.
D) The effect is predictable and universal – Incorrect; strain-dependent.
E) Can be exploited for combination therapy – Correct; beta-lactam + vancomycin.
✅ Correct: A, B, C, E
11. Which statements about colistin (polymyxin E) are correct?
A) Binds to lipopolysaccharide (LPS) and displaces calcium/magnesium – Correct; disrupts outer
membrane.
B) Dose-limiting nephrotoxicity occurs in up to 50% – Correct.
C) Neurotoxicity (paresthesias, ataxia, respiratory paralysis) – Correct; dose-related.
, D) Heteroresistance common – Correct; subpopulations with reduced susceptibility.
E) Monotherapy is preferred over combination – Incorrect; combination reduces resistance.
✅ Correct: A, B, C, D
12. Which statements about tigecycline are correct?
A) Glycylcycline derivative of minocycline – Correct.
B) Active against MRSA, VRE, MDR Acinetobacter, ESBL-producing Enterobacteriaceae – Correct.
C) Not active against Pseudomonas – Correct; intrinsic resistance due to efflux pumps.
D) High serum protein binding (71-89%) – Correct.
E) Associated with increased mortality in VAP (not indicated) – Correct; low lung levels.
✅ Correct: A, B, C, D, E
13. Which statements about eravacycline are correct?
A) Fluorocycline, synthetic tetracycline – Correct.
B) Active against tetracycline-resistant organisms (tetK, tetM) – Correct; overcomes common
resistance.
C) Active against Pseudomonas – Incorrect; like tigecycline, no Pseudomonas.
D) FDA-approved for complicated intra-abdominal infections – Correct.
E) Less nausea than tigecycline – Correct; improved GI tolerability.
✅ Correct: A, B, D, E
14. Which statements about omadacycline are correct?
A) Aminomethylcycline, oral and IV – Correct.
B) Once-daily dosing – Correct.
C) Active against MRSA, VRE, S. pneumoniae, Legionella – Correct.
D) Not active against Pseudomonas or Proteus – Correct.
E) Can be taken with dairy or antacids (no chelation) – Correct; unique among tetracyclines.
✅ Correct: A, B, C, D, E
15. Which statements about lefamulin are correct?
A) Pleuromutilin antibiotic, inhibits peptidyl transferase – Correct.
B) First-in-class oral for community-acquired pneumonia – Correct.
C) Active against macrolide- and fluoroquinolone-resistant S. pneumoniae – Correct.
D) Avoid with CYP3A4 inducers (rifampin) – Correct; reduced efficacy.
E) QT prolongation risk – Correct; mild to moderate.