The in vitro activity of ertapenem against bacterial pathogens isolated from patients with moderate to severe complicated intra-abdominal, complicated skin/skin structure, acute pelvic, or complicated urinary tract infection or community acquired pneumonia was compared to ceftriaxone and piperacillin-tazobactam and related to known plasma concentrations of the three agents. Ertapenem was more potent against methicillin-susceptible Staphylococcus aureus (MSSA) than ceftriaxone and piperacillin-tazobactam and was more potent and more active than both of these agents against Enterobacteriaceae and anaerobes. Piperacillin-tazobactam was the most active agent against enterococci and Pseudomonas aeruginosa. All isolates of Enterobacteriaceae (n=1088), Streptococcus pyogenes (n=37), Streptococcus agalactiae (n=48), MSSA (n=187), Haemophilus influenzae (n=59), and Moraxella catarrhalis (n=9) were susceptible to ertapenem; < 1% of 1284 anaerobes and only 1 of 113 Streptococcus pneumoniae (a penicillin-resistant isolate) were resistant to ertapenem. The MIC value at which 90% of all Enterobacteriaceae, streptococci, MSSA, H. influenzae, M. catarrhalis, and anaerobes were inhibited (MIC90) was < or = 1 microg/ml and below the mean plasma concentration of total ertapenem following a 1 g intravenous infusion for at least 24 hours, i.e., the entire recommended dosing interval, and below the free drug concentration for at least 8 h.