A major global study has found a statistically significant association between the commonly prescribed antibiotic cefepime and a higher risk of all-cause mortality compared to other beta-lactam antibiotics. The research, published in JAMA Network Open, analyzed 110 randomized clinical trials involving more than 22,000 patients who received either cefepime or another beta-lactam antibiotic, such as penicillins or cephalosporins.
The study reported 778 deaths among 11,726 patients (6.6%) treated with cefepime, compared to 6.2% among those given alternative antibiotics. Researchers evaluated deaths occurring within approximately 30 days of treatment. Using a Bayesian meta-analysis, they calculated a 94.4% probability that cefepime was associated with higher mortality. When restricted to 73 peer-reviewed trials, the probability increased to 98.6%.
The association was more pronounced in adults than children and strongest among patients treated for febrile neutropenia—a severe condition marked by fever and dangerously low white blood cell counts. The drug remains widely used in clinical settings to treat bacterial infections, including pneumonia, urinary tract infections (UTIs), skin infections, and meningitis.
How the drug works and its risks
Cefepime is a fourth-generation cephalosporin antibiotic administered via injection, typically in hospitals or clinical settings. It is part of the beta-lactam class, which also includes widely used antibiotics like penicillin and amoxicillin. According to the Mayo Clinic, severe side effects may include confusion, decreased consciousness, or seizures, particularly in older adults and patients with kidney problems. Common symptoms may also include gastrointestinal issues, rash, or allergic reactions.
Study scope and patient populations
The research reviewed trials involving patients treated for a range of conditions, including:
- Febrile neutropenia
- Pneumonia
- Severe bacterial infections
- Urinary tract infections (UTIs)
- Meningitis
Both adults and children were included in the analysis, though the elevated risk was more apparent in adult populations. The study did not examine long-term outcomes beyond the 30-day window.
What experts say
The findings suggest a potential need for heightened monitoring when prescribing cefepime, particularly for vulnerable populations such as older adults or those with pre-existing kidney conditions. However, the study does not establish causation—only an association between the drug and increased mortality risk. Clinical guidelines continue to recommend cefepime for certain severe infections where its benefits may outweigh risks.
The U.S. Food and Drug Administration (FDA) has not issued new warnings regarding cefepime as of the study’s publication. Healthcare providers are advised to follow existing prescribing information and consider patient-specific factors when selecting antibiotics.