An evaluation of the in vitro activity of piperacillin/tazobactam

Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as Bacteroides species. Its combination with piperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were determined for 1952 individual patient isolates of Gram positive and negative bacteria causing significant infections and compared with MIC values for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1992). Piperacillin/tazobactam had excellent activity against methicillin susceptible staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiella species. Activity against Gram negative organisms capable of producing chromosomally mediated beta-lactamases was good, since in most organisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were derepressed hyperproducing mutants; these isolates showed resistance to piperacillin/tazobactam since tazobactam does not inhibit these Class I beta lactamases. Activity was superior to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam has a suitable spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as aspiration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episodes in immunosuppressed patients.