title: 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 To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials.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.affiliation: Office of Antimicrobial Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. peter.kim@fda.hhs.gov
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kim
authors.forename: Yu-te
authors.initials: YT
authors.lastname: Wu
authors.forename: Charles
authors.initials: C
authors.lastname: Cooper
authors.forename: George
authors.initials: G
authors.lastname: Rochester
authors.forename: Thamban
authors.initials: T
authors.lastname: Valappil
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kornegay
authors.forename: Sumathi
authors.initials: S
authors.lastname: Nambiar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000401:mortality*; D000077723:Cefepime; D002511:Cephalosporins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D005335:Fever of Unknown Origin / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000401:mortality; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000401:mortality; D016019:Survival Analysis; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000401:mortality; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime