High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales with Moderate to High Risk of Clinically Significant AmpC β-lactamase Production

Ashlan J. Kunz Coyne, Amer El Ghali, Kristen Lucas, Paige Witucki, Nicholas Rebold, Dana J. Holger, Michael P. Veve, Michael J. Rybak

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background. Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4–8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. Methods. This was a retrospective cohort study of hospitalized patients with E. cloacae, K. aerogenes, or C. freundii bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates. Results. Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79–2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52–1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04–1.92), deep infection (aHR, 2.27; 95% CI, 1.21–4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03–1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40–0.89). Conclusions. Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy.

Original languageEnglish
Article numberofad034
JournalOpen Forum Infectious Diseases
Issue number3
StatePublished - Mar 1 2023

Bibliographical note

Funding Information:
Potential conflicts of interest. M.J.R. has received funds for research and consulting or participated in speaking bureaus for AbbVie, Contrafect, Entasis, Ferring, Melinta, Merck, Paratek Pharmaceuticals, Shionogi, Spero, Tetraphase, and T2 Bioscience and is partially supported by National Institute of Allergy and Infectious Diseases R01 AI121400 and R21 AI163726. All other authors report no potential conflicts.

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.


  • ampC β-lactamase-producing Enterobacterales
  • antimicrobial stewardship
  • bacteremia
  • carbapenem
  • cefepime
  • propensity score
  • time-varying analysis

ASJC Scopus subject areas

  • Oncology
  • Infectious Diseases


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