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.