title: Tazobactam is a potent inactivator of selected inhibitor-resistant class A beta-lactamases.
abstract: The beta-lactam beta-lactamase inhibitor combinations (ampicillin/clavulanate, ampicillin/sulbactam, ticarcillin/clavulanate and piperacillin/tazobactam) were tested against selected inhibitor-resistant class A beta-lactamases of the TEM and OHIO-1 varieties. Minimum inhibitor concentrations (MIC) revealed that the Escherichia coli DH5 alpha transconjugate strains that possessed the OHIO-1 beta-lactamase, Met69Ile mutant of the OHIO-1 beta-lactamase, TEM-30 (Arg244Ser) and TEM-31 (Arg244Cys) beta-lactamase were most susceptible to piperacillin and piperacillin/tazobactam. Kinetic experiments with each beta-lactamase demonstrated that tazobactam was 10-25-fold more potent than clavulanate or sulbactam against TEM-30 and TEM-31 beta-lactamase. Tazobactam was also as effective as clavulanate against the Met69Ile mutant of the OHIO-1 beta-lactamase. Among the clinically available beta-lactams and beta-lactamase inhibitors, piperacillin/tazobactam appears to be the most potent combination against selected inhibitor-resistant strains of TEM and OHIO-1 beta-lactamase.
authors.affiliation: Research Service, Department of Veterans Affairs Medical Center, Cleveland, OH, USA. rab14@po.cwru.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: S A
authors.initials: SA
authors.lastname: Rudin
authors.forename: D M
authors.initials: DM
authors.lastname: Shlaes
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000668:Ampicillin Resistance / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019818:Clavulanic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D000667:Ampicillin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin