Meta-analysis of a possible signal of increased mortality associated with cefepime use.

Abstract

BACKGROUND:

On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other beta-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials.

METHODS:

We performed meta-analyses using trial- and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method.

RESULTS:

The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21).

CONCLUSIONS:

In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials.

• Authors: Peter W Kim, Yu-te Wu, Charles Cooper, George Rochester, Thamban Valappil, Yan Wang, Cynthia Kornegay, Sumathi Nambiar
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 51 Issue 4 Pg. 381-9 (Aug 15 2010) ISSN: 1537-6591 [Electronic] United States
• PMID: 20624065 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Anti-Bacterial Agents
• Cephalosporins
• Cefepime

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (therapeutic use)
• Bacterial Infections (drug therapy, mortality)
• Cefepime
• Cephalosporins (therapeutic use)
• Child
• Child, Preschool
• Clinical Trials as Topic
• Female
• Fever of Unknown Origin (complications, drug therapy, mortality)
• Humans
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Neutropenia (complications, drug therapy, mortality)
• Pneumonia, Bacterial (drug therapy, mortality)
• Skin Diseases, Bacterial (drug therapy, mortality)
• Survival Analysis
• Urinary Tract Infections (drug therapy, mortality)
• Young Adult