Cefepime Linked to Higher Mortality Risk Than Other Beta-Lactams: Study
Canada: A systematic review and meta-analysis found that cefepime was associated with higher odds of all-cause mortality compared with other beta-lactam antibiotics. There was a 94.4% probability that cefepime was indeed associated with greater mortality. The mortality signal may be related to both underexposure and overexposure, given cefepime’s relatively narrow therapeutic window. Further research is needed to clarify this potential safety concern.
The systematic review and Bayesian meta-analysis, published in JAMA Network Open by Zahra N. Sohani, Division of Infectious Diseases and Medical Microbiology, Department of Medicine, Hôpital Maisonneuve-Rosemont, CIUSSS de l’Est-de-l’Île-de-Montréal, Montreal, Quebec, Canada, and colleagues, evaluated mortality outcomes associated with cefepime compared with other β-lactam antibiotics.
Cefepime is widely used for conditions including febrile neutropenia and infections caused by Gram-negative organisms with potential AmpC β-lactamase production. However, concerns about its safety have persisted, prompting researchers to examine mortality outcomes across randomized clinical trials.
The investigators searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and LILACS from inception through May 25, 2026. Eligible studies compared cefepime with another β-lactam in children or adults and reported all-cause mortality.
The analysis included 110 randomized clinical trials involving 22,608 patients. Of these, 11,726 received cefepime and 10,882 received a comparator β-lactam. Mortality occurred in 778 patients (6.6%) receiving cefepime compared with 674 (6.2%) in comparator groups.
Key findings included:
- Cefepime had a 94.4% posterior probability of being associated with higher mortality than other β-lactams.
- The pooled odds ratio was 1.10 (95% credible interval, 0.98–1.24).
- The estimated number needed to harm was between 111 and 227.
- Among 73 published peer-reviewed trials involving 15,411 patients, the probability of higher mortality with cefepime increased to 98.6% (OR, 1.17; 95% credible interval, 1.02–1.34).
- The trend toward higher mortality was generally observed across different comparator β-lactams, clinical indications and cefepime doses of 2 g or more every 12 hours.
The researchers noted that the findings should be interpreted cautiously. Many included studies were open-label, potentially allowing treatment modifications after randomization. Limited information from unpublished trials also restricted assessment of their methodology. In addition, all-cause mortality is a broad outcome that may reflect underlying illness, particularly among patients with cancer, rather than a specific drug-related mechanism.
The authors emphasized that the findings do not mean cefepime should be abandoned. Instead, the observed mortality signal supports careful consideration of its role in individual patients and highlights the need for prospective studies examining dosing strategies that balance antimicrobial effectiveness with safety.
Overall, the analysis suggests a potential mortality concern with cefepime compared with other β-lactams. Further research is warranted to determine whether optimized dosing can reduce potential harm and to inform future clinical guidelines.
Reference:
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
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