Cefepime Linked to Higher Mortality Odds

A systematic review and Bayesian meta-analysis found a 94.4% posterior probability that cefepime was associated with higher odds of all-cause mortality than other β-lactam antibiotics. The pooled estimate across all included trials was an odds ratio (OR) of 1.10 (95% credible interval [CrI], 0.98-1.24). The findings were published in JAMA Network Open.

Investigators included randomized clinical trials in adults or children that compared cefepime monotherapy with another β-lactam or cefepime plus a second drug with another β-lactam plus the same second drug. Trials of prophylactic cefepime and cefepime–β-lactamase inhibitor combinations were excluded. The primary outcome was all-cause mortality at 30 days or the closest reported time point.

The analysis included 110 trials and 22,608 patients: 11,726 received cefepime and 10,882 received a comparator β-lactam. Death occurred in 778 cefepime recipients (6.6%) and 674 comparator recipients (6.2%), corresponding to an absolute risk increase of 0.4 percentage points and an approximate number needed to harm of 227. Among 73 published peer-reviewed trials involving 15,411 patients, the posterior probability that the OR exceeded 1 was 98.6% (OR, 1.17; 95% CrI, 1.02-1.34), with an absolute risk increase of 0.9 percentage points and an approximate number needed to harm of 111.

The evidence base also included 12 abstract or unpublished reports and 25 FDA-provided trials. Adding unpublished studies attenuated the mortality estimate, and the FDA-provided trials yielded estimates in the opposite direction from the published literature. Investigators rated the certainty of evidence as moderate, downgrading it because of heterogeneity and possible publication bias.

Many trials were open label, and limited information about unpublished trials constrained assessment of their methods. The authors also noted that all-cause mortality is an imperfect safety outcome, particularly in patients with cancer. They characterized the result as a global safety signal rather than evidence of a specific causal mechanism and stated that it did not imply cefepime should no longer be used.

Source: Sohani ZN, Zhong YJ, Afshar A, et al. Cefepime and mortality: a systematic review and Bayesian meta-analysis. JAMA Netw Open. 2026;9(9):e2633017. doi:10.1001/jamanetworkopen.2026.33017