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JAC Advance Access published online on January 28, 2003

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg114
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Variable susceptibility to piperacillin/tazobactam amongst Klebsiella spp. with extended-spectrum {beta}-lactamases

Gioia S. Babini 1, Meifang Yuan 2, Lucinda M. C. Hall 2, David M. Livermore 1*

1 Antibiotic Resistance Monitoring & Reference Laboratory, Central Public Health Laboratory, 61 Colindale Avenue, London NW9 5HT
2 Barts & The London School of Medicine & Dentistry, Turner Street, London E1 2AD, UK

* Corresponding author. E-mail: Dlivermore{at}phls.nhs.uk.

Received 23 July 2002 ; revised 4 November 2002 ; accepted 26 November 2002

Abstract

MICs of piperacillin/tazobactam are conventionally determined by varying the concentration of piperacillin in the presence of a fixed 4 mg/L tazobactam. When tested in this way, the MIC distribution for Klebsiella isolates with extended-spectrum {beta}-lactamases (ESBLs) is strongly bimodal, such that many producers are inhibited at 16 + 4 mg/L whilst others require MICs of >=512 + 4 mg/L. When, however, piperacillin/tazobactam was tested as a fixed 8:1 ratio, the MIC distribution became unimodal. If clavulanate 4 mg/L was combined with piperacillin, a unimodal MIC distribution was seen for ESBL-producing Klebsiella spp. but a bimodal distribution arose if the clavulanate concentration was reduced to 0.25 mg/L. These data for alternative combinations suggested that the bimodal MIC distribution seen for piperacillin + tazobactam 4 mg/L was a titration effect, not a reflection of some ESBLs being resistant to tazobactam. Even within single strains, as defined by serotype and DNA fingerprints, there was considerable variation in susceptibility to piperacillin + tazobactam 4 mg/L, with some representatives highly susceptible and others highly resistant. Some of the more resistant representatives produced more of their ESBL, or had a greater number of {beta}-lactamase types, but these associations were not universal. Elevated resistance to piperacillin + tazobactam was not associated with porin change in any ESBL producer examined, but has been found by others.

Keywords: piperacillin/tazobactam, Klebsiella, extended-spectrum {beta}-lactamases
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