The Role of Cefepime in the Treatment of Extended-Spectrum Beta-Lactamase Infections

J Pharm Pract. 2019 Aug;32(4):458-463. doi: 10.1177/0897190017743134. Epub 2017 Nov 22.

Abstract

Objective: To review the efficacy of cefepime for use in infections caused by extended-spectrum beta-lactamase (ESBL)-producing organisms.

Data sources: A PubMed literature search (May 2000 to June 2017) was performed using the keyword cefepime and the MeSH terms beta-lactamases, cephalosporinases, and Enterobacteriaceae infections.

Study selection and data extraction: All human, English language studies evaluating cefepime use for the treatment of ESBL-producing Escherichia coli and Klebsiella pneumoniae infections were included.

Data synthesis: Studies assessing the use of cefepime for ESBL infections are few, and clinical studies are limited by design and sample size. The largest pharmacokinetic/pharmacodynamic study, a Monte Carlo simulation using data from the U.S. SENTRY antimicrobial surveillance program, evaluating cefepime use for infections due to ESBL-producing organisms found a 95% to 100% probability of target attainment with traditional cefepime dosing regimens. Most clinical studies found that patients treated with cefepime empirically and definitively had higher rates of mortality than those treated with carbapenems. However, in concordance with other studies reporting minimum inhibitory concentration (MIC) data, lower MICs were associated with lower mortality.

Conclusions: Cefepime should be avoided for empiric treatment of suspected ESBL infections and should only be considered for definitive treatment if the MIC ≤1 µg/mL. However, the site and severity of infection, local resistance patterns, and patient-specific risk factors should also help guide antimicrobial selection.

Keywords: Enterobacteriaceae infections; beta lactamases; cefepime; cephalosporinases.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Cefepime / administration & dosage*
  • Cefepime / pharmacology
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Cefepime
  • beta-Lactamases