PIPERACILLIN TAZOBACTAM - A REVIEW OF ITS ANTIBACTERIAL ACTIVITY, PHARMACOKINETIC PROPERTIES AND THERAPEUTIC POTENTIAL/

Combining tazobactam, a beta-lactamase inhibitor with the ureidopenici llin, piperacillin, successfully restores the activity of piperacillin against beta-lactamase-producing bacteria. Tazobactam has inhibitory activity, and therefore protects piperacillin against Richmond and Syk es types II, III, Nand V beta-lactamases, staphylococcal penicillinase and extended-spectrum beta-lactamases. However, tazobactam has only s pecies-specific activity against class I chromosomally-mediated enzyme s. Resistant organisms include some Citrobacter spp., Enterobacter spp ., Serratia spp., Xanthomonas maltophilia and Enterococcus faecium. Co nsistent with its in vitro activity, preliminary clinical data indicat e that the fixed combination of piperacillin/tazobactam (dose ratio 8: 1) is effective in the treatment of moderate to severe polymicrobial i nfections, including intra-abdominal, skin and soft-tissue and lower r espiratory tract infections. In limited comparative trials, piperacill in/tazobactam demonstrated equivalent or better efficacy than standard comparator regimens in these infections. Piperacillin/tazobactam in c ombination with an aminoglycoside was effective in the empirical treat ment of fever inpatients with neutropenia and compared favourably with ceftazidime in combination with an aminoglycoside, although second-li ne therapy with a glycopeptide antibiotic may be indicated in unrespon sive episodes. Data from phase III trials indicate that piperacillin/t azobactam has a tolerability profile typical of a penicillin agent. Pi peracillin/tazobactam provides a broad spectrum of antibacterial activ ity in a convenient single formulation suitable for use in the treatme nt of polymicrobial infections. Possible limitations concern its restr icted activity against class I beta-lactamases, enzymes that are becom ing increasingly important in the nosocomial environment. Combined the rapy with an aminoglycoside may be necessary in more serious infection s.