AN EVALUATION OF THE IN-VITRO ACTIVITY OF PIPERACILLIN TAZOBACTAM/

Tazobactam is a new, irreversible inhibitor of bacterial betalactamase s of staphylococci, plasmid-mediated beta-lactamases of the TEM and SH V types found in Escherichia coli and Klebsiella species and beta-lact amases of anerobes such as Bacteroides species. Its combination with p iperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SH V betalactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIG) of piperacillin/tazobactam were deter mined for 1952 individual patient isolates of Gram positive and negati ve bacteria causing significant infections and compared with MIC value s for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/cl avulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1 992). Piperacillin/tazobactam had excellent activity against methicill in susceptible staphylococci, Streptococcus pneumoniae, Haemophilus in fluenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pse udomonas aeruginosa isolates tested. It was not active against extende d spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiell a species. Activity against Gram negative organisms capable of produci ng chromosomally mediated beta-lactamases was good, since in most orga nisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were d erepressed hyper-producing mutants; these isolates showed resistance t o piperacillin/tazobactam since tazobactam does not inhibit these Clas s I beta lactamases. Activity was superior to ticarcillin/ clavulanic acid for Gram negative rods. Imipenem was the most active agent agains t ESBL producing Klebsiella species. Piperacillin/tazobactam has a sui table spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as asp iration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episo des in immunosuppressed patients.