Meta-Analysis of a Possible Signal of Increased Mortality Associated with Cefepime Use

• Published in: Clinical infectious diseases 2010-08, Vol.51 (4), p.381-389
• Main Authors: Kim, Peter W., Wu, Yu-te, Cooper, Charles, Rochester, George, Valappil, Thamban, Wang, Yan, Kornegay, Cynthia, Nambiar, Sumathi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibacterials; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; ARTICLES AND COMMENTARIES; Bacterial Infections - drug therapy; Bacterial Infections - mortality; Biological and medical sciences; Cephalosporins - therapeutic use; Child; Child, Preschool; Clinical trials; Clinical Trials as Topic; Comparators; Drug therapy; Experimentation; Female; Fever of Unknown Origin - complications; Fever of Unknown Origin - drug therapy; Fever of Unknown Origin - mortality; Humans; Infant; Infant, Newborn; Infections; Infectious diseases; Male; Medical sciences; Meta analysis; Middle Aged; Mortality; Neutropenia; Neutropenia - complications; Neutropenia - drug therapy; Neutropenia - mortality; Pathogens; Pharmacology. Drug treatments; Pneumonia; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - mortality; Skin Diseases, Bacterial - drug therapy; Skin Diseases, Bacterial - mortality; Survival Analysis; Urinary Tract Infections - drug therapy; Urinary Tract Infections - mortality; Young Adult
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/655131

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 β-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 To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials.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.