Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate

Abstract

The in vitro activities of ticarcillin, piperacillin, clavulanic acid, tazobactam, ticarcillin-clavulanate, and piperacillin-tazobactam against 819 bacterial isolates were compared. The two beta-lactamase inhibitors, clavulanic acid and tazobactam, had little useful antibacterial activity but enhanced the activities of the penicillins against beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and methicillin-susceptible Staphylococcus aureus; all strains were susceptible to both combinations. Both enzyme inhibitors also enhanced the activities of the penicillins against most strains of Escherichia coli, Klebsiella spp., Citrobacter diversus, Proteus spp., Providencia spp., and Bacteroides spp. and against occasional strains of Citrobacter freundii, Enterobacter spp., and Serratia marcescens. Clavulanic acid frequently enhanced the activity of ticarcillin against Xanthomonas maltophilia, and tazobactam frequently enhanced the activity of piperacillin against Morganella morganii. Enhancement was observed primarily with strains relatively resistant to the penicillins. In general, clavulanic acid was more effective than tazobactam in enhancing penicillin activity against Klebsiella spp., C. diversus, X. maltophilia, and Bacteroides spp., whereas tazobactam was more effective against Escherichia coli and Proteeae. There was little or no enhancement of activity against Enterococcus faecalis, Aeromonas hydrophila, Pseudomonas aeruginosa, Pseudomonas cepacia, or Acinetobacter anitratus. Clavulanic acid occasionally antagonized the activity of ticarcillin against ticarcillin-susceptible members of the family Enterobacteriaceae, but those strains were still considered susceptible to the combination. Tazobactam never antagonized the activity of piperacillin. In a direct comparison of the activities of ticarcillin-clavulanate and piperacillin-tazobactam, the two were equally active against H. influenzae, B. catarrhalis, and S. aureus; the latter was more active against E. faecalis. For relatively susceptible strains of members of the family Enterobacteriaceae, neither combination was predictably more active than the other, but relatively resistant strains were generally more susceptible to piperacillin-tazobactam. Piperacillin-tazobactam was more active than ticarcillin-clavulanate against A. hydrophila, P. aeruginosa, and P. cepacia, similar in activity against A. anitratus, and less active against X. maltophilia and Bacteroides spp.