A 62-year-old man is evaluated in the hospital on hospital day 3. He originally presented … — USMLE Step 2 CK

A $62$ -year-old man is evaluated in the hospital on hospital day $3$ . He originally presented with a $2$ -day history of fever, right flank pain, and dysuria. Medical history is significant for nephrolithiasis, for which he underwent a cystoscopy with stent placement $1$ week ago.

On admission, temperature was $38.9^\circ\text{C}$ ( $102.0^\circ\text{F}$ ), blood pressure was $104/62\text{ mmHg}$ , and pulse was $112/\text{min}$ . Laboratory studies showed a leukocyte count of $16,500/\mu\text{L}$ . He was empirically started on intravenous piperacillin-tazobactam.

Today (hospital day $3$ ), his temperature is $37.4^\circ\text{C}$ ( $99.3^\circ\text{F}$ ), blood pressure is $122/78\text{ mmHg}$ , and pulse is $84/\text{min}$ . Blood and urine cultures obtained on admission both grow *Enterobacter cloacae*. Antimicrobial susceptibility testing reveals the following:

* Ampicillin: Resistant
* Cefazolin: Resistant
* Ceftriaxone: Susceptible
* Cefepime: Susceptible
* Piperacillin-tazobactam: Susceptible
* Meropenem: Susceptible

Based on these results, which of the following is the most appropriate next step in the patient's antimicrobial management?

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

Answer

The correct answer is to transition the patient to intravenous cefepime.

The correct next step is to transition the patient to intravenous cefepime. *Enterobacter cloacae* is an organism that intrinsically carries an inducible chromosomal *AmpC* beta-lactamase gene. In the setting of a high initial bacterial burden or invasive infection (such as bacteremia), treating this organism with a third-generation cephalosporin (e.g., ceftriaxone) can rapidly select for derepressed mutants that hyperproduce the AmpC enzyme, leading to subsequent clinical failure despite initial in vitro susceptibility. Cefepime, a fourth-generation cephalosporin, is highly stable against AmpC hydrolysis and is a weak inducer of the enzyme. According to current infectious disease guidelines, cefepime is the preferred definitive therapy for susceptible, high-risk AmpC producers. This choice maximizes clinical efficacy while adhering to antibiotic stewardship principles by sparing carbapenems.

Step-by-Step Solution

Analyze the clinical scenario and the microbiological data.

The patient has a urinary-source bacteremia caused by *Enterobacter cloacae*. He is clinically improving on empiric therapy, but definitive targeted therapy is now required based on culture susceptibilities.

Establishing the severity (invasive bacteremia) and the specific pathogen dictates the rules of antibiotic stewardship.

Identify the specific resistance mechanisms characteristic of the isolated organism.

*Enterobacter cloacae* is a classic high-risk producer of inducible chromosomal AmpC beta-lactamase.

Organisms with AmpC (like Enterobacter, Klebsiella aerogenes, and Citrobacter freundii) can rapidly develop resistance on therapy even if they initially test susceptible to certain antibiotics.

Evaluate the treatment options for an AmpC-producing organism.

Third-generation cephalosporins (ceftriaxone) and piperacillin-tazobactam are associated with clinical failure in invasive AmpC infections despite in vitro susceptibility. Cefepime and carbapenems (meropenem) remain clinically active.

Selecting an antibiotic that will not be hydrolyzed by the AmpC enzyme is critical for patient survival.

Apply antimicrobial stewardship principles to select the definitive agent.

Cefepime should be selected over meropenem since the isolate is susceptible to cefepime.

Carbapenems should be spared whenever possible to prevent the emergence of carbapenem-resistant Enterobacteriaceae (CRE). Cefepime provides the optimal balance of targeted efficacy and stewardship.

Key Concept

Definitive treatment of invasive infections caused by high-risk AmpC-producing Enterobacterales (e.g., *Enterobacter cloacae*) requires cefepime (when susceptible) to avoid clinical failure and spare carbapenem use.

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