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Difficulty: HardInfectious Diseases

A 64-year-old man is evaluated in the intensive care unit on hospital day 3. He was admitted with septic shock secondary to an obstructing right ureteral calculus. A percutaneous nephrostomy tube was placed shortly after admission. Empiric therapy with intravenous vancomycin and meropenem was initiated. Today, his temperature is 37.2∘C37.2^\circ\text{C} (99.0∘F99.0^\circ\text{F}), blood pressure is 118/74 mmHg118/74\text{ mmHg}, and pulse is 82/min82/\text{min}. Vasopressors were weaned off yesterday. Blood and urine cultures obtained at admission both grow *Enterobacter cloacae*. Susceptibility testing results for both isolates are as follows:

Antimicrobial AgentResult
AmpicillinResistant
CeftriaxoneSusceptible
CefepimeSusceptible
MeropenemSusceptible
Piperacillin-tazobactamSusceptible
CiprofloxacinResistant
Trimethoprim-sulfamethoxazoleResistant

Based on these results and the patient's clinical improvement, which of the following is the most appropriate next step in pharmacotherapy?

  1. Cease vancomycin and initiate intravenous cefepimeAnswer
  2. B
    Cease vancomycin and initiate intravenous ceftriaxone
  3. C
    Cease vancomycin and initiate intravenous piperacillin-tazobactam
  4. D
    Cease vancomycin and continue intravenous meropenem
  5. E
    Continue the current regimen of vancomycin and meropenem without alteration

Answer

The correct step is to discontinue vancomycin and transition to intravenous cefepime.
The correct decision involves two key stewardship actions: stopping unnecessary Gram-positive coverage (vancomycin) and narrowing Gram-negative coverage from a carbapenem to a safe, effective alternative. For invasive infections caused by AmpC-producing organisms (like Enterobacter cloacae), cefepime is the preferred carbapenem-sparing agent because its structural properties render it stable against AmpC beta-lactamase hydrolysis. By de-escalating to cefepime, the clinician effectively treats the bacteremia while preserving carbapenems.

Step-by-Step Solution

1
Analyze the culture and susceptibility results to identify the pathogen and its resistance profile.
The patient has bacteremia and bacteriuria caused by Enterobacter cloacae.
Accurate identification is required to tailor empiric antimicrobial therapy to definitive, targeted therapy.
2
Assess the intrinsic resistance mechanisms characteristic of the isolated organism.
Enterobacter cloacae is a known AmpC beta-lactamase producing organism.
Organisms with chromosomal ampC genes (such as Enterobacter, Klebsiella aerogenes, and Citrobacter freundii) can rapidly develop resistance to third-generation cephalosporins during therapy.
3
Apply antimicrobial stewardship principles to select the most appropriate definitive agent.
Cefepime is selected because it is stable against AmpC hydrolysis, while vancomycin is stopped due to lack of Gram-positive organisms, and meropenem is stopped to spare carbapenem use.
Optimizing definitive therapy requires balancing clinical efficacy, patient safety, and the prevention of broad-spectrum antimicrobial resistance.

Key Concept

Management of invasive AmpC beta-lactamase producing organisms (e.g., Enterobacter cloacae) requires avoiding third-generation cephalosporins (like ceftriaxone) due to the risk of inducible resistance, and utilizing effective carbapenem-sparing agents (like cefepime) to optimize antimicrobial stewardship.
Estimated Time:1m 45s
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Infectious Diseases

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