Complex Clonal and Plasmid Epidemiology in the First Outbreak of Enterobacteriaceae Infection Involving VIM-1 Metallo-Beta-Lactamase in Spain: Toward Endemicity?

Clin Infect Dis. 2007 Nov 1;45(9):1171-8. doi: 10.1086/522288. Epub 2007 Sep 27.


Background: We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain).

Methods and results: During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, < or = 1 to > 8 microg/mL), as were aminoglycosides and ciprofloxacin. The bla(VIM-1) MBL gene was present in all isolates; in addition, the bla(SHV-12) extended-spectrum beta-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla(VIM-1) gene was detected within a 4.0-kb class 1 integron (bla(VIM-1)-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla(VIM-1)-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla(VIM-1) gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300- or 435-kb belonging to IncH12 group were found among E. cloacae isolates.

Conclusions: K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla(VIM-1) gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Cloning, Molecular
  • Disease Outbreaks*
  • Drug Resistance, Multiple, Bacterial
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / enzymology
  • Enterobacteriaceae Infections / epidemiology*
  • Enterobacteriaceae Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • Spain / epidemiology
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism


  • Anti-Bacterial Agents
  • beta-Lactamases