Cefepime Side Effects May Increase Risk of Death: Study

Researchers say the potential mortality risk may involve both inadequate cefepime exposure and neurotoxicity at higher doses.

The findings of a new study suggest that cefepime, one of the most commonly used antibiotics in hospitals, may be associated with a higher risk of death than other similar antibiotics.

According to findings published September 10 in JAMA Network Open, researchers analyzed data from more than 22,000 patients and found a 94.4% probability that cefepime was associated with higher all-cause mortality than other beta-lactam antibiotics.

However, the researchers did not recommend abandoning cefepime. Instead, they said the potential mortality signal should be considered when determining how the antibiotic is used in clinical practice, particularly given concerns about both inadequate drug exposure and neurotoxicity at higher doses.

Cefipime Side Effects

Formerly sold under the brand name Maxipime, cefepime is an intravenous cephalosporin antibiotic used to treat serious bacterial infections affecting the lungs, skin, abdomen, bloodstream and other parts of the body. It was approved by the U.S. Food and Drug Administration (FDA) in 1996 and remains widely used in hospital settings.

In 2012, the FDA warned about a risk of seizures among patients receiving Maxipime, particularly nonconvulsive status epilepticus, a potentially life-threatening neurological complication.

Additional concerns emerged in 2023, when researchers linked cefepime to other neurological problems, including convulsions, agitation and delirium. The findings suggested cefepime may cross the blood-brain barrier and cause neurotoxicity, potentially leading to serious complications such as delirium, coma and seizures.

Those risks have also surfaced in litigation. One lawsuit alleged an Ohio woman died after receiving a high dose of cefepime that doctors should have recognized as potentially toxic for her.

Cefepime Death Risks

For the new study, researchers from the University of Montreal in Quebec, Canada, conducted a meta-analysis of 110 randomized clinical trials covering 22,608 patients. Led by Dr. Zahra N. Sohani, the team focused on studies comparing cefepime use with other similar beta-lactam antibiotics.

Data indicated cefepime was associated with a 94.4% probability of higher mortality compared with other beta-lactam antibiotics, with deaths occurring among 6.6% of patients receiving cefepime, compared with 6.2% of those given similar antibiotics.

Overall, researchers estimated there was one additional death for every 227 patients treated with cefepime. When the analysis was limited to peer-reviewed, published trials, there was a 98.6% probability that cefepime was associated with higher mortality, representing approximately one additional death for every 111 patients treated.

The strongest mortality signal was seen among patients treated for febrile neutropenia, a condition marked by high fever in individuals with abnormally low levels of neutrophils, a type of white blood cell. In those instances, researchers found a 96.1% probability that cefepime was associated with a higher risk of death than other beta-lactam antibiotics.

The findings also suggested the risk increased with higher doses, with a 93.7% probability of increased mortality among patients receiving at least 2 grams every 12 hours and a 94.6% probability among those receiving at least 2 grams every eight hours.

Researchers said there were two possibilities for the increased risk of death. Either patients were being undertreated or overtreated. If undertreated, the initial condition is not fully resolved and may increase the risk of death. In other cases, patients may be given too much of the antibiotic, which could lead to neurotoxicity.

“These findings suggest that the potential mortality signal associated with cefepime should be considered when framing its role in clinical practice guidance.”

— Dr. Zahra N. Sohani, Cefepime and Mortality: A Systematic Review and Bayesian Meta-Analysis

Despite the risks, researchers emphasized that doctors should not stop prescribing cefepime. Instead, they should weigh the risks for the patient and the necessity for treatment.

Sign up for more health and legal news that could affect you or your family.