title: Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by gram-negative organisms.
abstract: For commonly encountered gram-negative bacilli, a MIC of cefepime of 8 mug/ml or less was defined by the Clinical and Laboratory Standards Institute as "susceptible" prior to the commercial release of the antibiotic. We assessed 204 episodes of bacteremia caused by gram-negative organisms for which patients received cefepime (typically 1 to 2 g every 12 h) as the primary mode of therapy. The cefepime MIC breakpoint derived by classification and regression tree (CART) software analysis to delineate the risk of 28-day mortality was 8 microg/ml. Patients infected with gram-negative organisms treated with cefepime at a MIC of > or =8 microg/ml had a mortality rate of 54.8% (17/31 died), compared to 24.1% (35/145 died) for those treated with a cefepime MIC of <8 microg/ml. The rate of mortality for those treated with a cefepime MIC of 8 microg/ml was 56.3% (9/16 died), compared to 53.3% (8/15 died) for those treated with cefepime at a MIC of >8 microg/ml. A multivariable analysis including severity of illness indices showed that treating patients with bacteremia due to gram-negative organisms with a cefepime MIC of > or =8 microg/ml was an independent predictor of mortality (P < or = 0.001). There was no significant difference in outcome according to the dosage regimen utilized. Pharmacodynamic assessments that were presented previously would suggest that cefepime treatment (particularly a dosage of 1 g every 12 h) has a low probability of target attainment associated with successful in vivo outcome when the cefepime MIC is > or =8 microg/ml. It would appear reasonable, based on pharmacodynamic and clinical grounds, to lower the breakpoints for cefepime in countries where the cefepime dosage of 1 to 2 g every 12 h is the licensed therapy for serious infections, so that organisms with a cefepime MIC of 8 microg/ml are no longer regarded as susceptible to the antibiotic.
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh Medical Center, Suite 3A Falk Medical Building, 3601 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Bhat
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Shutt
authors.forename: Blair
authors.initials: B
authors.lastname: Capitano
authors.forename: Brian A
authors.initials: BA
authors.lastname: Potoski
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime