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Difficulty: Very hardInfectious Diseases

A 6464-year-old man is evaluated in the intensive care unit for a persistent fever. He was admitted 88 days ago for a severe exacerbation of chronic obstructive pulmonary disease and required endotracheal intubation on the second day of admission. Four days ago, he developed a new fever, worsening oxygenation, and thick endotracheal secretions. Blood and lower respiratory tract cultures were obtained, and empiric therapy with intravenous piperacillin-tazobactam and vancomycin was initiated. Today, his temperature is 38.7∘C38.7^\circ\text{C} (101.7∘F101.7^\circ\text{F}), blood pressure is 112/68 mm Hg112/68\text{ mm Hg}, pulse is 102/min102/\text{min}, and leukocyte count is 16,500/mm316,500/\text{mm}^3. Blood cultures have remained sterile. The endotracheal aspirate culture grows \textit{Enterobacter cloacae}. Antimicrobial susceptibility testing shows the isolate is susceptible to ceftriaxone, ceftazidime, cefepime, piperacillin-tazobactam, and meropenem, but resistant to ampicillin and cefazolin. Which of the following is the most appropriate next step in the pharmacologic management of this patient?

  1. Intravenous cefepime monotherapyAnswer
  2. B
    Intravenous ceftriaxone monotherapy
  3. C
    Intravenous meropenem monotherapy
  4. D
    Intravenous piperacillin-tazobactam monotherapy
  5. E
    Continue the current empiric regimen

Answer

The most appropriate next step is to initiate targeted therapy with intravenous cefepime monotherapy. Vancomycin should be discontinued, and piperacillin-tazobactam should be switched to cefepime to avoid inducible resistance while adhering to antibiotic stewardship principles.
The patient has ventilator-associated pneumonia caused by \textit{Enterobacter cloacae}. \textit{E. cloacae} is a classic high-risk organism known to possess an inducible chromosomal AmpC beta-lactamase gene (often remembered as part of the SPACE or HECK-Yes mnemonic). The standard of care for serious infections caused by these organisms is a fourth-generation cephalosporin, such as cefepime. Cefepime is highly stable against hydrolysis by AmpC beta-lactamases and effectively treats the infection while avoiding the unnecessary use of carbapenems. Furthermore, since there is no evidence of a Gram-positive infection, empiric vancomycin must be promptly discontinued.

Step-by-Step Solution

1
Identify the primary site of infection and offending pathogen
Hospital-acquired ventilator-associated pneumonia caused by Enterobacter cloacae.
The patient developed a new fever, thick secretions, and respiratory deterioration 4 days after intubation, with the respiratory culture growing heavy E. cloacae.
2
Determine the resistance risk profile of the isolated pathogen
E. cloacae is a high-risk AmpC beta-lactamase producing organism.
SPACE (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter) organisms possess inducible chromosomal AmpC beta-lactamase genes.
3
Evaluate the current empiric antibiotic regimen
Vancomycin should be discontinued; piperacillin-tazobactam is suboptimal for definitive therapy.
No MRSA or other Gram-positive pathogens were isolated, rendering vancomycin unnecessary. Piperacillin-tazobactam is not recommended for severe AmpC infections.
4
Select the optimal definitive therapy based on stewardship guidelines
Cefepime is the preferred agent.
Cefepime is stable against AmpC hydrolysis. Ceftriaxone carries a high risk of inducing resistance, and meropenem should be spared unless the isolate is cefepime-resistant.

Key Concept

AmpC Beta-Lactamase Inducible Resistance and Antibiotic Stewardship
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Topics

Infectious Diseases

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