Cefepime: Out of the Doghouse
Special Commentary
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
In response to a published metanalysis that concluded that cefepime use was associated with excess mortality,1 on November 14, 2007, the FDA published an "Early Communication About an Ongoing Safety Review of Cefepime (marketed as Maxipime)."2 While not confirming the results of that metanalysis, it indicated it was reviewing the subject, and estimated that it would reach a conclusion in approximately four months. Well after four months had elapsed, it issued a statement indicating it was having difficulty accessing all the relevant information. The FDA has now, 19 months after its original missive, published a statement that, for all practical purposes, exonerates cefepime.3
The FDA performed meta-analyses using data in addition to the 38 clinical trials examined by Yahav et al,1 in which patients were subjected to only a trial-level meta-analysis. The FDA, in contrast, performed metaanalyses using both trial-level and patient-level data, and found no statistically significant differences in mortality in patients given cefepime relative to those given comparator antibiotics (see Table). A subset analysis of trials involving patients with febrile neutropenia also showed no statistically significant difference in mortality (adjusted risk difference = 9.67 per 1,000 population [95% CI, -2.87 to 22.21]).
The methodology of Yahav et al was recently examined with the conclusion of their finding that increased mortality associated with cefepime use was unreliable.4 Yahav et al, however, caution that administration of this antibiotic may be associated with an increased risk of encephalopathy. Encephalopathy has previously been reported with cefepime, as it has with other β-lactam antibiotics, and it frequency may be greatest in patients with renal insufficiency. Thus, Garces et al found that 5 of 498 cefepime recipients developed encephalopathy, which was associated with reduced renal function.5 This suggests that this complication is concentration- and dose-dependent.
References:
- Yahav D, et al. Efficacy and safety of cefepime: A systematic review and meta-analysis. Lancet Infect Dis. 2007:7:338-348.
- FDA. http://www.fda.gov/Drugs/DrugSafety
- Information for Healthcare Professionals: Cefepime (marketed as Maxipime) FDA ALERT [06/17/2009]. http://www.fda.gov/Drugs/DrugSafety
- Nguyen TD, et al. Cefepime therapy and all-cause mortality. Clin Infect Dis. 2009;48:902-904.
- Garces EO, et al. Renal failure is a risk factor for cefepime-induced encephalopathy. J Nephrol. 2008;21:526-534.
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