The in vitro activity of piperacillin/tazobactam and several comparison broad-spectrum compounds was assessed against recent clinical isolates of Gram-positive and -negative bacteria from geographically diverse medical centers in Europe, North and Latin America participating in various surveillance programs in 2000. Several organisms were characterized for phenotypic expression of various resistant determinants such as extended-spectrum beta-lactamase (ESBL) or amp C cephalosporinase hyperproduction, and vancomycin resistance in enterococci (VRE). Piperacillin/tazobactam retained activity (MIC50) against oxacillin-susceptible Staphylococcus spp. (0.12-0.5 microg/ml), Bacillus spp. (0.5 microg/ml), vancomycin-susceptible enterococci (>4 microg/ml), and Corynebacterium spp. (2 microg/ml; not including C. jeikeium) with susceptibility rates of 100.0, 91.7, 85.7 and 81.8%, respectively. Piperacillin/tazobactam inhibited all Streptococcus spp. strains at < or = 16 microg/ml, including penicillin-resistant strains many of which were co-resistant to erythromycin (90%) and other beta-lactams. A specific breakpoint for these streptococci when testing piperacillin/tazobactam appears needed to prevent false-resistant reports using penicillin as a class representative. The carbapenems among beta-lactams were the most active agents against the ESBL-producing species of Escherichia coli and Klebsiella pneumoniae and those strains which hyper-express amp C enzymes including Citrobacter spp. and Enterobacter spp. Piperacillin/tazobactam only exhibited modest activity against the "amp C resistance group" strains (68.8% susceptible or intermediate, MIC < or = 64 microg/ml). Piperacillin/tazobactam (MIC50, 8 microg/ml; 79.5% susceptible) was the most active agent tested against multi-drug resistant isolates of Pseudomonas aeruginosa. Against sampled Haemophilus influenzae (39.2% ampicillin-resistant), piperacillin/tazobactam (MIC(90,) < or = 0.06 microg/ml), ceftriaxone and ceftazidime inhibited 100.0% of the isolates at < or = 0.25 microg/ml. These in vitro surveillance results from the year 2000 on three continents, demonstrated a sustained potent activity of piperacillin/tazobactam against selected problematic nosocomial and community-acquired pathogens. The potential importance of these findings is that this beta-lactamase inhibitor combination can be used an empiric treatment of serious infections in hospital environments where resistance has emerged, as well as covering nearly all isolates of fastidious respiratory tract pathogens acquired in the community setting.