title: Susceptibility of beta-lactamase-producing enterococci to piperacillin with tazobactam.
abstract: The in vitro activity of piperacillin with and without tazobactam was evaluated against different inocula of 12 clinical isolates of beta-lactamase-producing Enterococcus faecalis obtained from different geographic areas. Minimum inhibitory concentrations (MICs) of piperacillin alone at approximately 10(3) colony-forming units (CFU)/spot ranged from 4 to 8 and from 4 to 8 micrograms/ml with piperacillin plus tazobactam. When approximately 10(7) CFU/spot was used, MICs increased to a range of 128-1024 micrograms/ml piperacillin. This inoculum effect was reversed by the addition of tazobactam to piperacillin at a fixed concentration of 1 microgram/ml or at a ratio of 8 : 1 (piperacillin relative to tazobactam) with an MIC90 of 16/2 micrograms/ml for the combination drug. In time-kill studies, four beta-lactamase-producing (Bla+) isolates were tested and demonstrated a decrease of > or = 2 log10 with 8 or 16 micrograms/ml of piperacillin in combination with 4 micrograms of tazobactam, but not with piperacillin alone. A non-beta-lactamase-producing isolate was equally inhibited by piperacillin alone and piperacillin plus tazobactam. Against a Bla+ isolate, the combination of piperacillin with tazobactam with streptomycin resulted in a synergistic effect relative to that of piperacillin with tazobactam; piperacillin plus streptomycin did not show synergism. Piperacillin in combination with tazobactam is active against enterococci that produce beta-lactamase and, in combination with an appropriate aminoglycoside, could be a viable choice for therapy of enterococci that do not have high-level resistance to all aminoglycosides.
authors.affiliation: Center for Infectious Diseases, University of Texas Medical School at Houston 77030.
authors.forename: P C
authors.initials: PC
authors.lastname: Okhuysen
authors.forename: K V
authors.initials: KV
authors.lastname: Singh
authors.forename: B E
authors.initials: BE
authors.lastname: Murray
mesh_terms: D003470:Culture Media; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010403:Penicillin Resistance; D010878:Piperacillin / Q000494:pharmacology*; D000077725:Piperacillin, Tazobactam Drug Combination; D013307:Streptomycin / Q000494:pharmacology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
chemical_list: D003470:Culture Media; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin; D013307:Streptomycin