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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Original article
1 Antibiotic Resistance
Monitoring & Reference Laboratory, Central Public Health
Laboratory,
61 Colindale Avenue, London NW9 5HT
* Corresponding author. E-mail: Dlivermore{at}phls.nhs.uk.
Received 23 July 2002
; revised 4 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
Keywords: piperacillin/tazobactam, Klebsiella,
extended-spectrum Variable susceptibility to piperacillin/tazobactam
amongst Klebsiella spp. with extended-spectrum
-lactamases
2 Barts & The London School of Medicine & Dentistry,
Turner Street, London E1 2AD, UK
-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
-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.
-lactamases
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