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Antimicrob. Agents Chemother. doi:10.1128/AAC.01487-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Failure of current cefepime breakpoints to predict clinical outcomes from Gram negative bacteremia

Division of Infectious Diseases, The University of Pittsburgh Medical Center, Suite 3A Falk Medical Building, 3601 Fifth Avenue, Pittsburgh, PA 15213; Beth Israel Deaconness Medical Center, Boston MA; Albany Medical Center, Albany NY

^* To whom correspondence should be addressed. Email: david.antibiotics{at}gmail.com.

	Abstract

For commonly encountered Gram negative bacilli, a minimal inhibitory concentration (MIC) of cefepime of 8 µg/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 Gram negative bacteremia for which patients received cefepime (typically 1-2 grams every 12 hours) as the primary mode of therapy. The cefepime MIC breakpoint derived by CART analysis to delineate the risk of 28 day mortality was 8 µg/mL. Patients with organisms with cefepime MICs 8 µg/mL had 54.8% mortality (17/31 died) compared to 24.1% (35/145 died) for those with cefepime MICs < 8 µg/mL. Mortality in those with a cefepime MIC of 8 µg/mL was 56.3% (9/16 died) compared to 53.3% (8/15 died) for those with cefepime MIC > 8 µg/mL. A multivariable analysis including severity of illness indices showed that cefepime treatment of patients with bacteremia due to organisms with a cefepime MIC of 8 µg/mL was an independent predictor of mortality (p0.001). There was no significant difference in outcome according to the dosage regimen utilized. Previously presented pharmacodynamic assessments would suggest that cefepime treatment (particularly if 1 gram every 12 hours is chosen) has a low probability of target attainment associated with successful in vivo outcome when the cefepime MIC is 8 µg/mL. It would appear reasonable on pharmacodynamic and clinical grounds to lower the breakpoints for cefepime in countries where cefepime 1-2 grams every 12 hours is licensed therapy for serious infections so that organisms with a cefepime MIC of 8 µg/mL are no longer regarded as susceptible to the antibiotic.

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