This study compared the in vitro activities of ertapenem (Merck & Co., Inc.), ceftriaxone, amoxicillin-clavulanate, and piperacillin-tazobactam against 518 aerobic and facultative bacterial pathogens isolated from 340 patients with complicated skin and skin structure infections. Ciprofloxacin was also tested against Gram-negative isolates. Gram-positive cocci accounted for 68.1% of the aerobic bacteria; Staphylococcus aureus was the most common isolate (45.6%). The ertapenem MIC was < or = 2 microg/ml for 80.9% of isolates and > or = 8 microg/ml for 16.2% (including isolates of enterococci, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and other nonfermentative Gram-negative bacteria). Against methicillin-susceptible S. aureus, ertapenem had the most potent activity. Ertapenem was the most active drug against Enterobacteriaceae (100% susceptible), whereas amoxicillin-clavulanate was least active (66% susceptible). Piperacillin-tazobactam was the most active drug against P. aeruginosa (100% susceptible), followed by ciprofloxacin (87% susceptible). In summary, ertapenem was highly active in vitro against many aerobic and facultative bacterial pathogens commonly recovered from patients with complicated skin and skin structure infections.