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

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.