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Antimicrobial Agents and Chemotherapy, December 2001, p. 3548-3554, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3548-3554.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cefepime, Piperacillin-Tazobactam, and the Inoculum Effect in Tests with Extended-Spectrum beta -Lactamase-Producing Enterobacteriaceae

Kenneth S. Thomson* and Ellen Smith Moland

Center for Research in Antiinfectives and Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska 68178

Received 17 January 2001/Returned for modification 31 May 2001/Accepted 28 August 2001

There is little information about the clinical effectiveness of cefepime and piperacillin-tazobactam in the treatment of infections caused by extended-spectrum beta -lactamase (ESBL)-producing pathogens. Some inferences have been drawn from laboratory studies, which have usually involved only one or a few strains of ESBL-producing Klebsiella pneumoniae or Escherichia coli that produced only a limited range of ESBLs. Such studies are indirect, sometimes conflicting, indicators of efficacy. To extend previous laboratory findings, a study was designed to investigate organism-drug interactions by determining the in vitro activities of eight parenteral beta -lactam agents against 82 clinical and laboratory strains of Klebsiella, Escherichia, Enterobacter, Citrobacter, Serratia, Morganella, and Proteus species that produced 22 different ESBLs, alone or in combination with other beta -lactamases. Activities were determined in broth microdilution MIC tests using standard and 100-fold-higher inocula. An inoculum effect, defined as an eightfold or greater MIC increase on testing with the higher inoculum, was most consistently detected with cefepime, cefotaxime, and ceftriaxone and least frequently detected with meropenem and cefoteten. Piperacillin-tazobactam was intermediate between these two groups of agents. Although the inoculum effect is an in vitro laboratory phenomenon, if it has any predictive value in identifying increased risk of therapeutic failure in serious infections, these results support suggestions that cefepime may be a less-than-reliable agent for therapy of infections caused by ESBL-producing strains.

* Corresponding author. Mailing address: Center for Research in Antiinfectives and Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178. Phone: (402) 280-2921. Fax: (402) 280-1225. E-mail: kstaac{at}creighton.edu.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3548-3554, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3548-3554.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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