A widely used antibiotic, cefepime, has been linked to an increased risk of all-cause mortality in adults, according to a new study published in JAMA Network Open. Cefepime is a broad-spectrum antibiotic typically administered via injection to treat severe bacterial infections such as pneumonia, urinary tract infections, and skin infections.
The global study analyzed data from 110 randomized clinical trials involving over 22,000 patients. These patients, including adults and children, were treated for conditions including febrile neutropenia, pneumonia, severe bacterial infections, UTIs, and meningitis. The research compared outcomes for patients who received cefepime against those who received other beta-lactam antibiotics, a class that includes penicillins and cephalosporins.
Across all analyzed trials, 778 deaths (6.6%) occurred among 11,726 patients treated with cefepime, compared to a rate of 6.2% for those receiving other beta-lactam antibiotics. Researchers evaluated all-cause mortality within approximately 30 days of treatment.
Utilizing a Bayesian meta-analysis, the study found a 94.4% probability that cefepime was associated with higher all-cause mortality when compared to other beta-lactam antibiotics. This probability increased to 98.6% when the analysis was restricted to 73 peer-reviewed published trials. The association appeared more pronounced in adults than in children and was strongest among patients treated for febrile neutropenia.
Despite these findings, the researchers did not recommend discontinuing cefepime, which remains a common treatment for serious infections in hospitalized patients due to its effectiveness against a wide range of bacteria. They emphasized the need for further research and guidance to better understand the drug's safety profile.
The study proposed several potential explanations for the observed association, though no single cause was definitively identified. These include drug levels that might be too low for effective treatment or neurotoxicity resulting from excessively high drug levels. The researchers noted that achieving the correct dosage of cefepime can be challenging, as higher doses can enhance bacterial killing but also increase the risk of toxic side effects.
The study acknowledged limitations, including the combination of trials with varying designs, patient populations, dosing strategies, and comparison antibiotics, with some studies dating back several decades. The analysis identified an association rather than proving that cefepime directly caused the higher mortality.
Dr. Marc Siegel, a senior medical analyst, commented that the study highlights the importance of re-evaluating existing data. He suggested that determining the precise optimal dose, potentially with the aid of AI, could be crucial in mitigating risks and improving patient outcomes.