Antimicrobial activities of piperacillin alone and in combination with tazobactam against beta-lactamase-producing bacteria

Abstract

Tazobactam (YTR 830), a new beta-lactamase inhibitor, was evaluated for its effect in combination with piperacillin, a broad spectrum, but beta-lactamase sensitive, penicillin, against 14 common bacteria. A total of 1,086 clinical isolates from different clinical specimens were tested for beta-lactamase production by the rapid chromogenic cephalosporin method. Their susceptibilities to piperacillin alone and in combination with tazobactam in a ratio of 8:1 by the agar dilution method were evaluated. The percentage of beta-lactamase producing strains ranged from 14.5% to 100% in these tested species. In general, the beta-lactamase producers were more resistant to piperacillin than the beta-lactamase nonproducers with higher minimal inhibitory concentrations (MICs). For the beta-lactamase producers, tazobactam decreased the MICs of piperacillin prominently in methicillin-resistant Staphylococcus aureus, Neisseria gonorrhoeae, Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Morganella morganii, Salmonella species and Bacteroides fragilis, with a 4-fold or greater decrease in MIC50, MIC90 and the geometric mean of MIC. For Serratia marcescens and Pseudomonas aeruginosa, the MICs did not change after adding tazobactam. For other species, there was a moderate decrease in MICs. We conclude that tazobactam is an effective beta-lactamase inhibitor for increasing the antimicrobial activity of piperacillin against beta-lactamase producing strains of many species of bacteria.