Piperacillin/tazobactam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential

Abstract

Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin, piperacillin, successfully restores the activity of piperacillin against beta-lactamase-producing bacteria. Tazobactam has inhibitory activity, and therefore protects piperacillin against Richmond and Sykes types II, III, IV and V beta-lactamases, staphylococcal penicillinase and extended-spectrum beta-lactamases. However, tazobactam has only species-specific activity against class I chromosomally-mediated enzymes. Resistant organisms include some Citrobacter spp., Enterobacter spp., Serratia spp., Xanthomonas maltophilia and Enterococcus faecium. Consistent with its in vitro activity, preliminary clinical data indicate that the fixed combination of piperacillin/tazobactam (dose ratio 8:1) is effective in the treatment of moderate to severe polymicrobial infections, including intra-abdominal, skin and soft-tissue and lower respiratory tract infections. In limited comparative trials, piperacillin/tazobactam demonstrated equivalent or better efficacy than standard comparator regimens in these infections. Piperacillin/tazobactam in combination with an aminoglycoside was effective in the empirical treatment of fever in patients with neutropenia and compared favourably with ceftazidime in combination with an aminoglycoside, although second-line therapy with a glycopeptide antibiotic may be indicated in unresponsive episodes. Data from phase III trials indicate that piperacillin/tazobactam has a tolerability profile typical of a penicillin agent. Piperacillin/tazobactam provides a broad spectrum of antibacterial activity in a convenient single formulation suitable for use in the treatment of polymicrobial infections. Possible limitations concern its restricted activity against class I beta-lactamases, enzymes that are becoming increasingly important in the nosocomial environment. Combined therapy with an aminoglycoside may be necessary in more serious infections.