Inhibition of β-lactamases by tazobactam and in-vitro antibacterial activity of tazobactam combined with piperacillin

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Abstract
The in-vitro synergistic activity of tazobactam, a new .beta.-lactamase inhibitor, combined with piperacillin was tested against various .beta.-lactamase-producing strains. The .beta.-lactamase inhibitory activity of tazobactam against various known types of .beta.-lactamase was also tested in comparison with clavulanic acid or sulbactam. Tazobactam caused a remarkable reduction of the piperacillin MICs for penicillinase- and oxyiminocephalosporinase-producing strains and also showed a moderate synergistic effect against cephalosporinase-producing strains. The bactericidal activity of piperacillin was enhanced in combination with tazobactam. Tazobactam inhibited the penicillinases, and the oxyiminocephalosporinase produced by Proteus vulgaris, at low concentration. In these cases its activity was comparable with that of clavulanic acid and stronger than that of sulbactam. Tazobactam demonstrated a better inhibitory capability than sulbactam agianst the cephalosporinases tested. Tazobactam was able to inactivate intracellular .beta.-lactamase in Prot. vulgaris and Morganella morganii, conforming its ability to penetrate the cell membrane of these species.