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Cefepime Antibiotic Linked to Higher Death Risk in Major Global Study
A new analysis of 110 randomized trials involving more than 22,000 patients finds that cefepime, a widely used injectable antibiotic, is associated with a higher risk of all-cause mortality compared with other beta-lactam antibiotics, though researchers stop short of recommending its discontinuation.
A widely used injectable antibiotic has been linked to a higher risk of death in adults, according to a major global analysis published in JAMA Network Open. The study reviewed 110 randomized clinical trials involving more than 22,000 patients who received either cefepime or another beta-lactam antibiotic, a class that includes penicillins and cephalosporins.
Across all trials, 778 deaths occurred among 11,726 patients given cefepime, or 6.6 percent, compared with 6.2 percent among patients who received a different antibiotic. Researchers evaluated deaths from any cause occurring within roughly 30 days of treatment. Using a Bayesian meta-analysis, they found a 94.4 percent probability that cefepime was associated with higher all-cause mortality. When the analysis was limited to 73 peer-reviewed published trials, that probability rose to 98.6 percent.
The association appeared stronger in adults than in children and was most pronounced among patients treated for febrile neutropenia, a medical emergency involving fever and dangerously low levels of infection-fighting white blood cells. The trials also covered patients treated for pneumonia, severe bacterial infections, urinary tract infections and meningitis.
Cefepime remains a common broad-spectrum antibiotic for serious bacterial infections in hospitalized patients because it is effective against a wide range of bacteria. It is typically administered by injection in a clinical setting. Severe side effects can include confusion, decreased consciousness or seizures, particularly in older patients and those with kidney problems.
The researchers did not recommend discontinuing cefepime but called for additional guidance and research to better understand its safety profile. They said several factors could explain the observed association, though they were unable to identify a single cause. Possible explanations include drug levels too low to effectively treat the infection and neurotoxicity, which can occur when drug levels become too high.
Finding the right dose can be challenging, the researchers noted, because higher doses may improve the drug's ability to kill bacteria while also increasing the risk of toxic side effects. The study had several limitations. It combined clinical trials that differed in design, patient populations, dosing strategies and comparison antibiotics, with some studies dating back decades. The analysis also found an association, not proof that cefepime itself caused the higher mortality.
Dr. Marc Siegel, a senior medical analyst who was not involved in the research, said the study demonstrates the importance of re-reviewing and analyzing older studies. He noted that febrile neutropenia itself is a major cause of death in this population, making it often difficult to determine whether the treatment decreases or possibly increases that risk. A closer review of the data suggests that both underdosing and overdosing, rather than the drug itself, may be more closely linked to poorer outcomes, indicating that appropriate dosing may be the key. Siegel also suggested there may be a role for artificial intelligence in determining the exact right dose and assessing outcomes.
The findings add to a growing body of research examining the real-world safety of commonly prescribed medications. For clinicians, the study underscores the need to weigh the benefits of cefepime against its potential risks, particularly in vulnerable patients such as older adults and those with compromised immune systems. Further research is needed to clarify optimal dosing strategies and to identify which patients may be most at risk.
