The in vitro activity of doripenem against prevalent nonfermentative Gram-negative bacilli and Aeromonas spp. was evaluated. The collection comprised 14979 nonduplicate clinical isolates submitted during a global Doripenem Surveillance Program conducted from 2003 through 2007. Susceptibility tests were performed using the Clinical and Laboratory Standards Institute reference broth microdilution method and the susceptibility criteria of the US Food and Drug Administration. Doripenem (MIC(90), 8 and 4 microg/mL) was 2-fold more potent than imipenem (MIC(90), >8 and 8 microg/mL) and meropenem (MIC(90), >8 and 8 microg/mL) against Pseudomonas aeruginosa and other Pseudomonas spp., covering 77.2% and 82.9% of the isolates, respectively, at the breakpoint of <or=2 microg/mL. Against Acinetobacter spp., including Acinetobacter baumannii, imipenem showed slightly greater activity and potency (2-fold) than other carbapenems, though only 41.8% of A. baumannii were susceptible at breakpoint. Doripenem, imipenem, and meropenem exhibited similar and near-complete coverage (98.2-98.8% at <or=4 microg/mL) against Aeromonas spp. Rates of susceptibility to doripenem among P. aeruginosa isolates varied by geographic region, being highest in North America and lowest in Latin America (84.9% and 67.2% inhibited at <or=2 microg/mL, respectively). Infections caused by nonfermentative Gram-negative bacilli and Aeromonas spp. often occur in severely debilitated patients and may be associated with poor clinical outcomes; moreover, these organisms have a significant capacity to develop resistance. Given the limited treatment choices available, doripenem appears to offer potency and an enhanced spectrum of activity usable against these troublesome pathogens, particularly against P. aeruginosa.