A 68-year-old man with a history of benign prostatic hyperplasia is admitted to the hospit… — USMLE Step 2 CK

A 68-year-old man with a history of benign prostatic hyperplasia is admitted to the hospital with fever, severe left flank pain, and dysuria. His temperature is $39.4^\circ\text{C}$ ( $102.9^\circ\text{F}$ ), blood pressure is $100/60\text{ mmHg}$ , and heart rate is $110\text{/min}$ . Laboratory studies show a leukocyte count of $18,000\text{/mm}^3$ . He is empirically started on intravenous piperacillin-tazobactam and intravenous fluids.

On hospital day 3, the patient is clinically improved and afebrile. Blood and urine cultures drawn at admission both grow *Enterobacter cloacae*.

Antimicrobial susceptibility testing of the isolate reveals the following:
- Ampicillin: Resistant
- Cefazolin: Resistant
- Ceftriaxone: Sensitive (MIC $\leq 1\text{ }\mu\text{g/mL}$ )
- Cefepime: Sensitive (MIC $\leq 1\text{ }\mu\text{g/mL}$ )
- Piperacillin-tazobactam: Sensitive (MIC $4\text{ }\mu\text{g/mL}$ )
- Meropenem: Sensitive (MIC $\leq 0.25\text{ }\mu\text{g/mL}$ )

Which of the following is the most appropriate next step in the antimicrobial management of this patient?

Switch to intravenous cefepimeAnswer
B
Switch to intravenous ceftriaxone
C
Continue intravenous piperacillin-tazobactam
D
Switch to intravenous meropenem
E
Add intravenous gentamicin to the current regimen

Answer

Switch to intravenous cefepime

The correct action is to switch to intravenous cefepime. This patient has a severe infection caused by *Enterobacter cloacae*, a member of the ESCPM group of organisms (which includes *Enterobacter*, *Serratia*, *Citrobacter freundii*, *Providencia*, and *Morganella*). These bacteria inherently possess an inducible chromosomal *ampC* beta-lactamase gene. When treated with a third-generation cephalosporin (such as ceftriaxone), subpopulations of bacteria that hyperproduce the AmpC enzyme are rapidly selected for, leading to high rates of clinical failure despite initial in vitro testing showing susceptibility. Cefepime, a fourth-generation cephalosporin, is highly stable against AmpC hydrolysis and is considered the drug of choice. It appropriately steps down the antimicrobial spectrum from the empiric piperacillin-tazobactam while ensuring a high likelihood of clinical success.

Step-by-Step Solution

Identify the pathogen and its specific intrinsic resistance mechanisms.

Enterobacter cloacae is identified, which is a classic AmpC beta-lactamase producing organism (part of the ESCPM group).

Accurate pathogen identification dictates the limitations of interpreting standard susceptibility reporting.

Evaluate the clinical risk of using third-generation cephalosporins for this isolate.

Ceftriaxone carries a high risk of inducing AmpC hyperproduction and failing clinically, despite appearing sensitive in vitro.

Exposure to third-generation cephalosporins selects for derepressed mutants, leading to rapid clinical failure.

Select the most appropriate targeted therapy based on antimicrobial stewardship principles.

Cefepime is selected because it is stable against AmpC hydrolysis and provides a narrower spectrum than carbapenems or piperacillin-tazobactam.

To successfully cure the infection while minimizing the selection pressure for broader resistance mechanisms.

Key Concept

Management of AmpC beta-lactamase-producing organisms (like Enterobacter) requires avoiding 3rd-generation cephalosporins (e.g., ceftriaxone) due to the high risk of inducible resistance; cefepime (a 4th-generation cephalosporin) or carbapenems are preferred.

Estimated Time:1m 30s

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