The in vitro activity of doripenem was evaluated against a recent collection of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates (201 ESBL-producing Enterobacteriaceae [153 Escherichia coli and 48 Klebsiella pneumoniae] and 201 P. aeruginosa). Comparator agents included amikacin, tobramycin, ciprofloxacin, cefepime, cefotaxime, ceftazidime piperacillin-tazobactam, imipenem, and meropenem. Both doripenem and meropenem inhibited 100% of the ESBL-producing Enterobacteriaceae at a parts per thousand currency sign0.5 A mu g/mL. For these isolates, the MIC90 of doripenem (0.12 A mu g/mL) was 4-fold lower than that of imipenem (0.5 A mu g/mL). Against P. aeruginosa, the MIC90 of doripenem and meropenem was 2 A mu g/mL, 4-fold lower than that of imipenem (8 A mu g/mL). At an MIC of a parts per thousand currency sign2 A mu g/mL, doripenem, meropenem, and imipenem inhibited 90.5%, 89.6%, and 82.1% of P. aeruginosa isolates, respectively. Doripenem maintained activity against imipenem-nonsusceptible isolates of P. aeruginosa; at an MIC of a parts per thousand currency sign4 A mu g/mL, it inhibited 15 of the 25 isolates with MICs for imipenem of > 4 A mu g/mL. Doripenem is active against ESBL-producing Enterobacteriaceae and P. aeruginosa isolates. Its activity is similar to that of meropenem and slightly better than that of imipenem. The results of this study suggest that doripenem could be an alternative therapeutic agent for infections caused by these organisms.