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Antimicrobial Agents and Chemotherapy, May 2003, p. 1643-1646, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1643-1646.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics-Pharmacodynamics of Cefepime and Piperacillin- Tazobactam against Escherichia coli and Klebsiella pneumoniae Strains Producing Extended-Spectrum ß-Lactamases: Report from the ARREST Program

P. G. Ambrose,1* S. M. Bhavnani,1 and R. N. Jones2

Cognigen Corporation, Buffalo, New York,1 The JONES Group/JMI Laboratories, North Liberty, Iowa2

Received 5 April 2002/ Returned for modification 17 December 2002/ Accepted 10 February 2003

The frequency of resistance to ß-lactams among nosocomial isolates has been increasing due to extended-spectrum ß-lactamase (ESBL)-producing enteric bacilli. Although clinical outcome data are desirable, assessment of clinical efficacy has been limited due to the lack of a statistically meaningful number of well-documented cases. Since time above the MIC (T>MIC) is the pharmacokinetic-pharmacodynamic (PK-PD) measure that best correlates with in vivo activity of ß-lactams, a stochastic model was used to predict the probability of PK-PD target attainment ranging from 30 (P30) to 70% (P70) T>MIC, for standard dosing regimens of both piperacillin-tazobactam and cefepime against Escherichia coli and Klebsiella pneumoniae ESBL phenotypes. The P70/30 T>MIC for cefepime at 2 g every 12 h against E. coli and K. pneumoniae was 0.99/1.0 and 0.96/1.0 and for a regimen of 1 g every 12 h was 0.96/1.0 and 0.93/0.99, respectively. For piperacillin-tazobactam at 3.375 g every 4 h against E. coli and K. pneumoniae, the P70/30 T>MIC was 0.77/0.96 and 0.48/0.77 and for a regimen of 3.375 g every 6 h was 0.28/0.91 and 0.16/0.69, respectively. These data suggest that the probability of achieving T>MIC target attainment rates is generally higher with cefepime than with piperacillin-tazobactam for present-day ESBL-producing strains when one uses contemporary dosing regimens.

* Corresponding author. Mailing address: Division of Infectious Diseases, Cognigen Corporation, 395 Youngs Rd., Buffalo, NY 14221-5831. Phone: (716) 633-3463, ext. 302. Fax: (716) 633-7404. E-mail: paul.ambrose{at}cognigencorp.com.

Antimicrobial Agents and Chemotherapy, May 2003, p. 1643-1646, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1643-1646.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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