A widely used antibiotic has been linked to an increased risk of death in a major new analysis published in JAMA Network Open. The drug, cefepime, is a broad-spectrum beta-lactam antibiotic administered intravenously in hospitals to treat serious bacterial infections such as pneumonia, urinary tract infections, skin infections, and meningitis. It is also a standard treatment for febrile neutropenia, a life-threatening condition marked by fever and dangerously low white blood cell counts.
Global Study Analyzes Over 22,000 Patients Across 110 Trials
The research team conducted a Bayesian meta-analysis of 110 randomized clinical trials involving more than 22,000 patients. Participants included both adults and children receiving either cefepime or a comparator beta-lactam antibiotic—a class that includes penicillins and other cephalosporins.
Across all trials, 778 deaths occurred among 11,726 patients treated with cefepime, yielding a mortality rate of 6.6%. In comparison, the mortality rate for patients receiving other beta-lactam antibiotics was 6.2%. The analysis evaluated all-cause mortality occurring within approximately 30 days of treatment initiation.
The statistical model found a 94.4% probability that cefepime was associated with higher all-cause mortality compared to other beta-lactam antibiotics. When the analysis was restricted to 73 peer-reviewed published trials, that probability rose to 98.6%. The association appeared stronger in adult patients than in children and was most pronounced among those treated for febrile neutropenia.
Researchers Urge Caution, Not Discontinuation
Despite the findings, the study authors did not recommend discontinuing cefepime, which remains a critical tool for treating multidrug-resistant bacterial infections in hospitalized patients. Instead, they called for additional guidance and further research to better understand the drug’s safety profile and optimize its use.
The researchers noted several potential explanations for the observed association, though they could not identify a single definitive cause. Possible factors include:
- Subtherapeutic drug levels: Doses too low to effectively eradicate the infection.
- Neurotoxicity: Adverse neurological effects—such as confusion, decreased consciousness, and seizures—that can occur when drug levels become too high, particularly in older adults and patients with kidney impairment.
Finding the optimal dose of cefepime is clinically challenging. Higher doses may improve bacterial killing but simultaneously increase the risk of toxic side effects, creating a narrow therapeutic window.
Study Limitations Noted
The analysis carries important limitations. The pooled trials varied significantly in design, patient populations, dosing regimens, and comparator antibiotics, with some studies dating back several decades. Critically, the analysis demonstrates an association, not causation—it does not prove that cefepime itself caused the higher mortality.
Expert Commentary: Dosing Precision and AI Potential
Dr. Marc Siegel, Fox News senior medical analyst and clinical professor of medicine at NYU Langone Health, who was not involved in the research, emphasized the value of re-evaluating older clinical data.
“In this case, it correctly pointed out that febrile neutropenia (low white blood cell count with a fever) is itself a big cause of death in this population, making it often difficult to determine if the treatment (cefepime) decreases or possibly increases this risk,”
Siegel told Fox News Digital. He suggested that a closer review of the data indicates both underdosing and overdosing—rather than the drug molecule itself—may be more closely linked to poorer outcomes and higher mortality risk, underscoring that appropriate dosing may be the key factor.
“I also think there may be a role for AI here in determining the exact right dose, as well as assessing outcome,”
Siegel added, pointing to artificial intelligence as a potential tool for precision dosing and outcome prediction in future clinical practice.
The findings highlight the ongoing need for rigorous post-market surveillance of established antibiotics and the importance of individualized dosing strategies—particularly for vulnerable hospitalized patients—to maximize efficacy while minimizing harm.
