Examination Featuring Multifactorial Clinical Scenarios, Emerging Resistance, Pharmacogenomics,
and 2026 Guideline-Based Critical Thinking Exercises.
Questions 1–150 (Complex/Difficult Set — Complete)
1. A 68-year-old male with a prosthetic aortic valve and chronic kidney disease stage 4 (CrCl 25
mL/min) develops Enterococcus faecalis endocarditis. The isolate is susceptible to ampicillin (MIC 2
mcg/mL) but resistant to vancomycin (MIC >256 mcg/mL) and high-level gentamicin (MIC >500
mcg/mL). Which regimen is most appropriate?
A) Ampicillin 2g IV q4h + ceftriaxone 2g IV q12h
B) Ampicillin 2g IV q4h + gentamicin 1 mg/kg IV q8h
C) Linezolid 600 mg IV q12h
D) Daptomycin 12 mg/kg IV daily
Correct Answer: A) Ampicillin + ceftriaxone
Explanation: This is high-level aminoglycoside-resistant (HLAR) E. faecalis. Gentamicin cannot be used.
Ampicillin + ceftriaxone provides synergy without aminoglycosides. Daptomycin has poor efficacy
against E. faecalis. Linezolid is second-line for endocarditis.
2. A 45-year-old with Pseudomonas aeruginosa bacteremia is on cefepime 2g IV q8h. The MIC is 4
mcg/mL. After 48 hours, fever persists. A repeat blood culture is positive. What is the most
appropriate next step?
A) Increase cefepime to 2g IV q6h
B) Add tobramycin
C) Change to ceftazidime-avibactam
D) Change to meropenem
Correct Answer: D) Change to meropenem
Explanation: Cefepime MIC of 4 mcg/mL is in the susceptible-dose dependent (SDD) range per CLSI
(MIC 4-8 mcg/mL requires higher dose or alternative). Meropenem is active. Ceftazidime-avibactam is
for ESBL/KPC, not routine Pseudomonas.
,3. A 72-year-old with Clostridioides difficile infection has a third recurrence. She has a history of
severe anaphylaxis to metronidazole. Which of the following is the most effective and appropriate
long-term preventive strategy after treating the current episode with fidaxomicin?
A) Oral vancomycin 125 mg daily for 6 months
B) Bezlotoxumab 10 mg/kg IV once
C) Fecal microbiota transplant (FMT) via colonoscopy
D) Oral rifaximin 400 mg BID for 20 days
Correct Answer: C) FMT via colonoscopy
Explanation: For multiply recurrent C. diff (≥3 episodes), FMT has cure rates >90%. Bezlotoxumab
reduces recurrence but is not as effective as FMT for multiple recurrences.
4. A 34-year-old with Neisseria gonorrhoeae urethritis has a ceftriaxone MIC of 0.5 mcg/mL. Which
of the following is true regarding this isolate?
A) It is fully susceptible to ceftriaxone
B) It meets the CDC definition of decreased susceptibility
C) It requires dual therapy with azithromycin
D) It is resistant to all cephalosporins
Correct Answer: B) It meets the CDC definition of decreased susceptibility
Explanation: CDC defines decreased susceptibility to ceftriaxone as MIC ≥0.5 mcg/mL. These isolates
require higher dose ceftriaxone (1g) and test-of-cure.
5. A 55-year-old with Klebsiella pneumoniae carbapenemase (KPC)-producing bacteremia is started
on ceftazidime-avibactam. After 5 days, the patient develops breakthrough bacteremia with a new
isolate that is resistant to ceftazidime-avibactam (MIC >64 mcg/mL). What is the most likely
resistance mechanism?
A) Plasmid-mediated AmpC beta-lactamase
B) Modification of avibactam binding site in KPC enzyme (KPC-3 variant)
C) Overexpression of efflux pumps
D) Porin loss
Correct Answer: B) Modification of avibactam binding site in KPC enzyme
Explanation: Resistance to ceftazidime-avibactam in KPC producers is often due to mutations in the
KPC enzyme (e.g., KPC-3 variants) that reduce avibactam binding. This is an emerging problem.
,6. A 28-year-old with Mycoplasma genitalium is treated with moxifloxacin after azithromycin failure.
The patient returns with persistent symptoms. Resistance testing reveals macrolide resistance (erm
gene) and fluoroquinolone resistance (parC mutation S83I). What is the next best treatment?
A) Doxycycline 100 mg BID x14 days
B) Pristinamycin 1g QID x10 days (if available)
C) Lefamulin 600 mg BID x7 days
D) Minocycline 100 mg BID x14 days
Correct Answer: B) Pristinamycin 1g QID x10 days
Explanation: Dual-resistant M. genitalium is challenging. Pristinamycin has activity. Lefamulin is not
approved for Mgen. Doxycycline suppresses but rarely cures.
7. A 70-year-old with Staphylococcus aureus bacteremia is on vancomycin. The MIC is 1.5 mcg/mL by
broth microdilution. The patient has a CrCl of 45 mL/min. Which of the following is the most
appropriate vancomycin dosing strategy to achieve an AUC/MIC target of ≥400?
A) 15 mg/kg IV q12h
B) 20 mg/kg IV q24h
C) 15 mg/kg IV q8h with monitoring of trough at 15-20 mcg/mL
D) 20 mg/kg IV q12h with Bayesian software-guided AUC monitoring
Correct Answer: D) 20 mg/kg IV q12h with Bayesian software-guided AUC monitoring
Explanation: 2026 guidelines recommend AUC-guided dosing over trough-only. For MIC >1 mg/L,
higher doses are needed. Bayesian software is preferred for precision.
8. A 45-year-old with Escherichia coli pyelonephritis has a urine culture showing ESBL production.
The isolate is susceptible to nitrofurantoin (MIC 16 mcg/mL), fosfomycin (MIC 32 mcg/mL),
ciprofloxacin (MIC 0.25 mcg/mL), and meropenem (MIC 0.03 mcg/mL). Which agent is most
appropriate for oral step-down therapy after IV meropenem?
A) Nitrofurantoin
B) Fosfomycin
C) Ciprofloxacin
D) TMP-SMX
Correct Answer: C) Ciprofloxacin
Explanation: Despite ESBL, the isolate is ciprofloxacin-susceptible. Ciprofloxacin achieves high urine
and tissue levels. Nitrofurantoin and fosfomycin are not for pyelonephritis. TMP-SMX is not tested but
likely resistant.
, 9. A 62-year-old with Candida glabrata candidemia has an echinocandin MIC of 4 mcg/mL for
caspofungin. Which of the following is the most appropriate therapy?
A) Continue caspofungin and add fluconazole
B) Switch to micafungin
C) Switch to amphotericin B liposomal
D) Switch to anidulafungin
Correct Answer: C) Switch to amphotericin B liposomal
Explanation: C. glabrata with echinocandin MIC ≥4 mcg/mL is resistant to all echinocandins (cross-
resistance). Amphotericin B is the alternative. Fluconazole is often resistant.
10. A 50-year-old with Mycobacterium abscessus pulmonary disease is started on a regimen
including azithromycin, amikacin, cefoxitin, and tigecycline. Which adverse effect requires
immediate discontinuation of which drug?
A) Orange-red discoloration of tears (cefoxitin)
B) Vestibular toxicity (amikacin)
C) Nausea and vomiting (azithromycin)
D) Hyperpigmentation (tigecycline)
Correct Answer: B) Vestibular toxicity (amikacin)
Explanation: Amikacin causes vestibular toxicity (dizziness, ataxia) and cochlear toxicity. Significant
vestibular toxicity requires drug discontinuation. The other options are less emergent.
11. A 38-year-old with Burkholderia cepacia pneumonia in cystic fibrosis is on meropenem plus
tobramycin. The isolate is resistant to ceftazidime (MIC 64 mcg/mL) but susceptible to meropenem
(MIC 2 mcg/mL). What additional agent is recommended for synergy?
A) Levofloxacin
B) TMP-SMX
C) Chloramphenicol
D) Minocycline
Correct Answer: B) TMP-SMX
Explanation: B. cepacia is often treated with TMP-SMX as part of combination therapy. Meropenem +
TMP-SMX is a common regimen. Levofloxacin has variable activity.