Tazobactam is a potent inactivator of selected inhibitor-resistant class A β-lactamases

• Published in: FEMS microbiology letters 1997-03, Vol.148 (1), p.59-62
• Main Authors: Bonomo, R.A, Rudin, S.A, Shlaes, D.M
• Format: Article
• Language: English
• Subjects: Ampicillin - pharmacology; Ampicillin Resistance - physiology; Anti-Bacterial Agents - pharmacology; beta-Lactamase Inhibitors; Clavulanic Acid - pharmacology; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - enzymology; Inhibitor-resistant β-lactamase; Kinetics; Penicillanic Acid - analogs & derivatives; Penicillanic Acid - metabolism; Penicillanic Acid - pharmacology; Penicillins - pharmacology; Piperacillin; Piperacillin - pharmacology; Tazobactam
• ISSN: 0378-1097; 1574-6968
• DOI: 10.1016/S0378-1097(97)00013-X

The β-lactam β-lactamase inhibitor combinations (ampicillin/clavulanate, ampicillin/sulbactam, ticarcillin/clavulanate and piperacillin/tazobactam) were tested against selected inhibitor-resistant class A β-lactamases of the TEM and OHIO-1 varieties. Minimum inhibitor concentrations (MIC) revealed that the Escherichia coli DH5α transconjugate strains that possessed the OHIO-1 β-lactamase, Met 69Ile mutant of the OHIO-1 β-lactamase, TEM-30 (Arg 244Ser) and TEM-31 (Arg 244Cys) β-lactamase were most susceptible to piperacillin and piperacillin/tazobactam. Kinetic experiments with each β-lactamase demonstrated that tazobactam was 10-25-fold more potent than clavulanate or sulbactam against TEM-30 and TEM-31 β-lactamase. Tazobactam was also as effective as clavulanate against the Met 69Ile mutant of the OHIO-1 β-lactamase. Among the clinically available β-lactams and β-lactamase inhibitors, piperacillin/tazobactam appears to be the most potent combination against selected inhibitor-resistant strains of TEM and OHIO-1 β-lactamase.