We investigated the susceptibility of 694 Pseudomonas aeruginosa clinical isolates to nine antipseudomonal agents including doripenem. Test strains were collected from 23 Japanese medical facilities from 1992 to 2004. Doripenem showed a minimum inhibitory concentration for 90% of the organisms (MIC(90)) of 8 microg/mL, which was the lowest among the tested antipseudomonal agents. The MIC(90) of doripenem was 2-fold lower than that of meropenem, imipenem and amikacin and was > or =4-fold lower than that of piperacillin/tazobactam, ceftazidime, cefepime, ciprofloxacin and tobramycin. Amikacin showed the lowest rate of resistance against all clinical isolates (5.8%) followed by doripenem (7.1%). No remarkable changes were observed from 1992 to 2004 in the frequency of P. aeruginosa strains resistant to the tested agents, except for imipenem. Of 116 ceftazidime-resistant strains, from 44.0% to 50.8% were susceptible to the three carbapenems, but only 2.6% to cefepime. Of 138 imipenem-resistant strains, from 44.2% to 51.4% were susceptible to doripenem and both cephems, but 25.4% to meropenem. Doripenem was more active against imipenem- or ceftazidime-resistant strains than meropenem, although the activity of doripenem correlated well with that of meropenem. In conclusion, doripenem had the most potent in vitro activity against P. aeruginosa clinical isolates among the tested antibiotics. Considering the trend of antimicrobial resistance of the clinical isolates in well-focused surveillance, pseudomonal infections should be treated with appropriate chemotherapy using antimicrobial agents with potent antipseudomonal activity and low resistance rates, such as doripenem, in order to prevent the outbreak of resistant strains.
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