In a recent study published in JAMA Network Open, researchers re-examined data from a series of clinical trials and studies to investigate whether patients treated with cefepime were more likely to die than those treated with other β-lactam antibiotics.

After analyzing more than 100 randomized trials involving 22,608 patients, researchers found a 94.4% probability that cefepime was associated with higher odds of death than other β-lactam antibiotics. Across all the trials screened, death occurred in 6.6% of cefepime-treated patients and 6.2% of comparison-group patients.

Lingering safety concerns

Cefepime was approved for medical use in 1994, but a study raised concerns about its safety only after it had been in clinical practice for a decade. In 2007, a meta-analysis by Yahav et al. found that patients treated with cefepime had a 26% higher relative risk of death than those treated with other β-lactam antibiotics.

Further studies suggested two possible mechanisms, both related to drug exposure rather than cefepime itself. The first is underexposure, in which a lower-than-required dose is prescribed, leading to inadequate treatment. The other is overexposure, which could cause neurotoxicity, especially when kidney function is impaired or dosing is not adjusted.