Antibiotic Cefepime Linked to Higher Death Risk in Adults

Use of the antibiotic cefepime in adult patients is associated with a higher risk of death compared with other β-lactam classes, according to a systematic review published in the September edition of JAMA Network Open. The findings raise new questions about cefepime's place in guidelines for treating severe infections, especially in hospitals that rely on it as a last line of defense.

Of 11,726 patients who received cefepime, 778 people, or 6.6%, died. That figure was higher than in the group that received other β-lactam antibiotics, which recorded 6.2% deaths. The difference is equivalent to four additional deaths per 1,000 patients. Further analysis revealed that adults treated with cefepime had an 18% higher risk of death, while in children no significant difference was found between cefepime and other β-lactams.

Nevertheless, experts caution that the study's broad scope—spanning multiple countries, age groups, and diseases—makes causal interpretation complicated. David Michalik, a pediatric infectious disease specialist at Miller Children’s and Women’s Hospital, Long Beach, California, who was not involved in the review, said the findings are still worth heeding as a warning. “Cefepime remains a reliable choice when patients need broad-spectrum antibacterial therapy for life-threatening illness,” he told Medical News Today. “However, the wide range of patient conditions in the study makes it difficult to state that cefepime is directly more lethal than other β-lactams.”

Michalik also highlighted the difference between adult and pediatric patients that the review authors did not specifically explain. According to him, there are many confounding factors in the clinical trials analyzed, plus the complexity of conditions and pharmacokinetic differences in children, so it would be inaccurate to conclude that children have a protective factor adults lack. He also judged that condition categories such as febrile neutropenia and severe bacterial infection are hard to compare directly because those labels are subjective and overlap with other diagnoses such as pneumonia, meningitis, or urinary tract infection.

“All antibiotics should be used carefully, and both doctors and patients need to be clear about which antibiotic is being used and for what indication. We live in an era when multi-drug-resistant pathogens are widespread,” Michalik said.

The review recommends that the possible mortality signal linked to cefepime be taken into account when drafting clinical practice guidelines. For Indonesia, the findings are relevant given that cefepime is among the antibiotics in circulation and used in referral hospitals for severe infections. With antimicrobial resistance cases rising in Southeast Asia, including Indonesia, monitoring the use of broad-spectrum antibiotics is becoming increasingly crucial. Antibiotic stewardship policies already in place at a number of hospitals need to take this risk signal into account without ignoring the need for therapy in critically ill patients.

Going forward, the question is not simply whether cefepime should be avoided, but how to ensure its use is truly on target. More controlled follow-up studies are needed to separate the drug's effect from the severity of patients' illness. Meanwhile, clinicians are expected to weigh risks and benefits more carefully, especially as antibiotic options become more limited due to resistance. Otherwise, we risk losing one of our last weapons against deadly infections—not because the drug is ineffective, but because we realized its safety limits too late.