According to a new study published in the journal JAMA Network Open, the widely used fourth-generation antibiotic cefepime may be associated with an increased risk of mortality in patients.
Cefepime was approved for medical use in 1994 and is widely used to treat serious bacterial infections and febrile neutropenia. Compared with many other antibiotics, it is considerably more effective against resistant microorganisms. Nevertheless, researchers reanalyzed data from 110 randomized clinical trials to determine whether treatment with cefepime carries a higher risk than treatment with other beta-lactam antibiotics.
The researchers analyzed data from 22,608 patients and found a 94.4% probability that cefepime carries a higher risk of fatal outcomes compared with other beta-lactam antibiotics. Across the studies, mortality was reported in 6.6% of patients treated with cefepime, compared with 6.2% in the control group, which received other antibiotics.
Notably, the increased risk of mortality was observed exclusively in adults, while no similar trend was identified in children. Overall, the data suggest that approximately one additional fatal case occurs for every 227 patients treated with cefepime. However, when the researchers analyzed only data from published, peer-reviewed studies involving 15,411 patients, the probability of increased mortality rose to 98.6%, corresponding to approximately one additional fatal case for every 111 patients.
The highest probability of increased risk (96.1%) was observed among patients with febrile neutropenia. Regarding dosage, the probability of harm exceeded 93% with standard and high doses (2 grams every 12 hours or more), while lower doses still carried an 80.5% probability of increased risk. The medication-related risks are primarily associated with two mechanisms: inadequate dosing, which can result in ineffective treatment of the infection, and excessive dosing, which may cause neurotoxicity in the presence of impaired kidney function.
The scientists emphasize that these findings should not be considered grounds for abandoning the drug, as cefepime remains a first-line defense against life-threatening conditions and infections caused by multidrug-resistant pathogens. However, the study authors urge the medical community to take these findings into account when developing clinical guidelines. Future research should determine to what extent individualized dosing and close monitoring of kidney function can improve patient safety.
