title: Is cefepime safe for clinical use? A Bayesian viewpoint.
abstract: Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections and complicated intra-abdominal infections. A recent meta-analysis by Yahav et al. (Lancet Infect Dis 2007; 7: 338-48) concluded that cefepime was associated with a statistically significant increase in mortality (risk ratio 1.26, 95% confidence interval 1.08-1.49) when compared with other antibiotics. The US FDA decided to re-evaluate the meta-analysis data in collaboration with the drug sponsor. Two years later the FDA Alert summarized that 'data do not indicate a higher rate of death in cefepime-treated patients. Cefepime remains an appropriate therapy for its approved indications.' However, a thorough evaluation of the 52-page FDA report still shows that safety remains an unresolved issue. A Bayesian re-appraisal of the findings by the FDA and by Yahav et al. indicates that there is a 90.9% (by FDA trial-level meta-analysis), 80.8% (by FDA patient-level meta-analysis) and 99.2% (by Yahav et al. meta-analysis) probability that cefepime raises mortality in neutropenic fever patients, which translates into the following numbers needed to harm (NNH), i.e. to cause one extra death with the use of cefepime: FDA trial-level meta-analysis, NNH = 109; FDA patient-level meta-analysis, NNH = 76; Yahav et al. meta-analysis, NNH = 54. A similar harmful probability was observed with skin structure infections but not with pneumonias, intra-abdominal infections and urinary tract infections. In conclusion, cefepime should be avoided in patients with neutropenic fever or with skin structure infections.
authors.affiliation: Infectious Diseases Division, University of Nebraska Medical Center, Omaha, NE 68198-5400, USA. akalil@unmc.edu
authors.forename: Andre C
authors.initials: AC
authors.lastname: Kalil
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000401:mortality*; D000077723:Cefepime; D002511:Cephalosporins / Q000009:adverse effects* / Q000627:therapeutic use*; D005335:Fever of Unknown Origin / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D015994:Incidence; D009503:Neutropenia / Q000188:drug therapy / Q000401:mortality; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000401:mortality; D013223:Statistics as Topic; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime