title: Variable susceptibility to piperacillin/tazobactam amongst Klebsiella spp. with extended-spectrum beta-lactamases.
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 > or =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.
authors.affiliation: Antibiotic Resistance Monitoring & Reference Laboratory, Central Public Health Laboratory, 61 Colindale Avenue, London NW9 5HT, UK.
authors.forename: Gioia S
authors.initials: GS
authors.lastname: Babini
authors.forename: Meifang
authors.initials: M
authors.lastname: Yuan
authors.forename: Lucinda M C
authors.initials: LM
authors.lastname: Hall
authors.forename: David M
authors.initials: DM
authors.lastname: Livermore
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology*; D006801:Humans; D007709:Klebsiella / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology*; D000077725:Piperacillin, Tazobactam Drug Combination; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D001618:beta-Lactamases; D010878:Piperacillin