Occurrence of PER-1 producing clinical isolates of Pseudomonas aeruginosa in Japan and their susceptibility to doripenem

J Antibiot (Tokyo). 2006 Dec;59(12):791-6. doi: 10.1038/ja.2006.104.

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.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology*
  • Ceftazidime / pharmacology
  • Doripenem
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / isolation & purification*
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Ceftazidime
  • Doripenem
  • beta-lactamase PER-1
  • beta-Lactamases