Piperacillin combined with tazobactam at a fixed concentration (4 micrograms/ml) and a ratio (8:1) was tested against 5,029 aerobic isolates and 447 fastidious organisms, including anaerobes. Among the Enterobacteriaceae, > 95% inhibition was shared only by imipenem (99.1% at < or = 4 micrograms/ml), and some newer cephalosporins (95.1% - 99.8% at < or = 8 micrograms/ml), and piperacillin-tazobactam (95.8% at < or = 16/4 micrograms/ml). Piperacillin-tazobactam was the most active agent tested against nonenteric Gram-negative bacilli (93.5% at < or = 8 micrograms/ml). Ampicillin-sulbactam was the most active agent against staphylococci (95.0% at < or = 8 micrograms/ml), followed by imipenem (91.8%), piperacillin-tazobactam (89.3% at < or = 8/4 micrograms/ml), and cefepime (86.2% at < or = 8 micrograms/ml). Against the enterococci, only ampicillin (93.0% at < or = 8 micrograms/ml) with or without sulbactam, piperacillin (91.0% at < or = 16 micrograms/ml) with or without tazobactam, and imipenem (91.0%) had acceptable activity. Piperacillin-tazobactam and imipenem were the most active drugs tested against all aerobic isolates, inhibiting 93.5% of isolates each. Piperacillin-tazobactam inhibited all fastidious isolates tested, including Haemophilus influenzae (MIC90, 0.094/4 micrograms/ml), Moraxella catarrhalis (MIC90, 0.064/4 micrograms/ml), Neisseira gonorrhoeae (MIC90, < or = 0.016/4 micrograms/ml), and Streptococcus pneumoniae (all MICs, < or = 4/4 micrograms/ml). Against the anaerobic isolates, the most broad-spectrum antimicrobial agents tested were imipenem (100.0%), piperacillin-tazobactam (99.5% at < or = 32/4 micrograms/ml), metronidazole (98.4% at < or = 8 micrograms/ml), and ticarcillin-clavulanic acid (95.1% at < or = 32/2 micrograms/ml). These results are nearly identical to a previous study involving the same five medical centers in 1989. Piperacillin-tazobactam appears to remain a highly effective beta-lactamase inhibitor combination with a wide empiric spectrum and potency in teaching hospitals.