Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections

Eur J Clin Microbiol Infect Dis. 2024 Feb;43(2):213-221. doi: 10.1007/s10096-023-04715-5. Epub 2023 Nov 23.

Abstract

Purpose: Cefepime is recommended for treating infections caused by AmpC beta-lactamase-producing Enterobacterales (AmpC-PE), though supporting evidence is limited. Therefore, this study compared outcomes associated with cefepime versus carbapenem therapy for bloodstream infections (BSIs) caused by AmpC-PE after phenotypic exclusion of ESBL-co-producing isolates.

Methods: This retrospective cohort study compared definite cefepime versus carbapenem treatment for AmpC-PE BSI in hospitalized patients of the University Hospital Basel, Switzerland, between 01/2015 and 07/2020. Primary outcomes included in-hospital death, renal impairment and neurologic adverse events; secondary outcomes included length of hospital stay and recurrent infection.

Results: Two hundred and seventy episodes of AmpC-PE BSI were included, 162, 77 and 31 were treated with a carbapenem, cefepime and other antibiotics, respectively. Patients treated with carbapenems were more likely to be transferred to the ICU on admission and more frequently had central venous catheter as a source of infection. In uni- and multivariable analyses, primary and secondary outcomes did not differ between the two treatment groups, except for more frequent occurrence of neurological adverse events among patients treated with carbapenems and shorter length of hospital stay among survivors treated with cefepime.

Conclusion: After excluding isolates with phenotypic ESBL-co-production, cefepime was not associated with adverse outcomes compared to carbapenems when used to treat BSIs caused by AmpC-PE. Our study provides evidence to support the use of cefepime as a safe treatment strategy for AmpC-PE BSI, particularly in clinically stable patients without initial renal impairment or increased susceptibility to neurological adverse events.

Keywords: AmpC beta-lactamase; Bloodstream infection; Carbapenem-sparing regimen; Cefepime; Enterobacterales.

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Bacterial Proteins*
  • Carbapenems / adverse effects
  • Cefepime / adverse effects
  • Cephalosporins / adverse effects
  • Enterobacteriaceae Infections* / drug therapy
  • Enterobacteriaceae Infections* / microbiology
  • Gammaproteobacteria*
  • Hospital Mortality
  • Humans
  • Microbial Sensitivity Tests
  • Retrospective Studies
  • Sepsis* / drug therapy
  • beta-Lactamases

Substances

  • Cefepime
  • AmpC beta-lactamases
  • Anti-Bacterial Agents
  • Carbapenems
  • Cephalosporins
  • beta-Lactamases
  • Bacterial Proteins