Is cefepime safe for clinical use? A Bayesian viewpoint

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberdkr138
Pages (from-to)1207-1209
Number of pages3
JournalJournal of Antimicrobial Chemotherapy
Volume66
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Meta-Analysis
Intraabdominal Infections
Skin
Urinary Tract Infections
Mortality
Pneumonia
Fever
Infection
Febrile Neutropenia
cefepime
Odds Ratio
Confidence Intervals
Anti-Bacterial Agents
Safety
Therapeutics
Pharmaceutical Preparations

Keywords

  • Adverse events
  • Cephalosporin
  • Statistics

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Is cefepime safe for clinical use? A Bayesian viewpoint. / Kalil, Andre C.

In: Journal of Antimicrobial Chemotherapy, Vol. 66, No. 6, dkr138, 01.06.2011, p. 1207-1209.

Research output: Contribution to journalArticle

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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.",
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