JAC Advance Access originally published online on January 28, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 605-612
© 2003 The British Society for Antimicrobial Chemotherapy
Variable susceptibility to piperacillin/tazobactam amongst Klebsiella spp. with extended-spectrum ß-lactamases
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
Received 23 July 2002; returned 4 November 2002; revised 22 November 2002; accepted 26 November 2002
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 ß-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 ß-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 ß-lactamases
* Present address. BD Diagnostic, PO Box 13, Denderstraat 24, B9320 Erembodegem, Belgium.
Present address. Vascular Biology Group, University Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK.
¶ Corresponding author. Tel: +44-20-8200-4400; Fax: +44-20-8358-3292; E-mail: Dlivermore{at}phls.nhs.uk
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