title: Occurrence of PER-1 producing clinical isolates of Pseudomonas aeruginosa in Japan and their susceptibility to doripenem.
abstract: The acquisition of resistance by extended-spectrum beta-lactamases (ESBL) has been reported primarily for Enterobacteriaceae, but there are few reports on the isolation of ESBL-producing Pseudomonas aeruginosa. PER-1-type ESBL producing P aeruginosa has been found in various regions around the world but there are no reports of clinical isolates in Japan. During our susceptibility surveillance studies over a 10 year period, we found four clinical isolates resistant to ceftazidime due to production of PER-1. They were resistant to ceftazidime but susceptible in the presence of clavulanic acid, a class A beta-lactamase inhibitor. The strains had the ability to hydrolyze ceftazidime. They also had the gene for PER-1-type ESBL. This is the first report of the isolation of PER-1 producing strains in Japan. These four strains were resistant to ceftazidime, cefepime and aztreonam with MICs of 64 microg/ml or more, but were more susceptible to carbapenem antibiotics. In particular, doripenem, which is a novel carbapenem antibiotic, showed good antibacterial activity with a MIC of 2 or 4 microg/ml, which was more potent than meropenem and imipenem. Doripenem also showed good therapeutic efficacy against a systemic infection of mice with a PER-1 producing strain, and was also more potent in vivo than imipenem or meropenem.
authors.affiliation: Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan. yoshinori.yamano@shionogi.co.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamano
authors.forename: Toru
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Takaji
authors.initials: T
authors.lastname: Fujimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Yutsudou
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Tsuji
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology; D000077726:Doripenem; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification*; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002442:Ceftazidime; D000077726:Doripenem; C108863:beta-lactamase PER-1; D001618:beta-Lactamases