Regional Outbreak of CTX-M-2 β-lactamase-producing Proteus Mirabilis in Japan

J Med Microbiol. 2012 Dec;61(Pt 12):1727-1735. doi: 10.1099/jmm.0.049726-0. Epub 2012 Aug 30.


Proteus mirabilis is a common cause of urinary tract infection. Wild-type P. mirabilis strains are usually susceptible to penicillins and cephalosporins, but occurrences of P. mirabilis producing extended-spectrum β-lactamases (ESBLs) have been recently reported. Here, we surveyed the prevalence of cefotaxime resistance among P. mirabilis strains at seven different hospitals in Kanagawa Prefecture, Japan, and investigated their molecular epidemiology to explain the mechanism of their spread. The prevalence of cefotaxime resistance among P. mirabilis increased annually, from 10.1 % in 1998 to 23.1 % in 2003, and increased drastically in 2004, exceeding 40 %. We collected 105 consecutive and non-duplicate cefotaxime-resistant P. mirabilis isolates (MIC 16 to >256 µg ml(-1)) from these hospitals from June 2004 to May 2005 and characterized their profile. PCR and sequence analysis revealed that all resistant strains produced exclusively CTX-M-2 β-lactamase. PFGE analysis identified 47 banding patterns with 83 % or greater similarity. These results indicated that a regional outbreak of P. mirabilis producing CTX-M-2 β-lactamase has occurred in Japan and suggest that the epidemic spread occurred within and across hospitals and communities by extended clonal strains. Plasmid analysis revealed that 44.8 % of plasmids harboured by bla(CTX-M-2) isolates had common profiles, encoding ISEcp1, IS26 and Int1, and belonged to incompatibility group T. Spread of the resistant isolates in Japan resulted from dissemination of narrow-host-range plasmids of the IncT group encoding bla(CTX-M-2). These findings indicate the rapidly developing problem of treating the species to prevent dissemination of ESBL producers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Cefotaxime / pharmacology*
  • Cross Infection
  • DNA, Bacterial / genetics
  • Disease Outbreaks*
  • Humans
  • Japan / epidemiology
  • Microbial Sensitivity Tests
  • Molecular Epidemiology
  • Plasmids
  • Proteus Infections / drug therapy
  • Proteus Infections / epidemiology*
  • Proteus Infections / microbiology
  • Proteus mirabilis / drug effects*
  • Proteus mirabilis / enzymology
  • Proteus mirabilis / isolation & purification
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*


  • Anti-Bacterial Agents
  • DNA, Bacterial
  • beta-lactamase CTX-2
  • beta-Lactamases
  • Cefotaxime