Cefepime Versus Carbapenem Therapy for the Treatment of Invasive Infections With Inducible Chromosomal AmpC-Producing Enterobacterales: A Systematic Review and Meta-analysis.

BACKGROUND

The optimal antibiotic choice for AmpC-producing Enterobacterales bloodstream infections (BSIs) and complicated urinary tract infections (cUTIs) remains to be clearly defined. Guidance from the Infectious Diseases Society of America recommends cefepime as first-line therapy, based on observational studies. We conducted a systematic review and meta-analysis to compare the clinical outcomes of cefepime versus carbapenems in patients with infections caused by AmpC-producing Enterobacterales.

METHODS

A systematic search was conducted across Medline, Embase, Cochrane, and Scopus databases to identify studies comparing cefepime and carbapenems for the treatment of BSIs and cUTIs due to AmpC-producing Enterobacterales. Eligible studies reported all-cause mortality as the primary outcome. Secondary outcomes included clinical and microbiological cure, relapse, and adverse events. A random-effects meta-analysis was performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS

Seven studies on BSI encompassing 1099 patients were included, with 479 receiving cefepime and 620 receiving carbapenem as definitive antibiotics. There were no studies on cUTI. No statistically significant difference in all-cause mortality was observed between cefepime and carbapenem treatment (log OR, 0.15 [95% CI, -.33 to .64]; = .54), although a nonsignificant trend favored cefepime, particularly in the subgroup of larger observational studies (n ≥ 50 patients) and more recent studies (published after 2019). Relapse rates were also comparable between the 2 groups (log OR, 0.39 [95% CI, -.25 to 1.03]; = .23).

CONCLUSIONS

In line with published guidance, treatment outcomes with cefepime did not differ significantly from carbapenems for AmpC-producing BSIs. However, randomized controlled trials are needed to validate these findings. PROSPERO: CRD42025634449.