title: Complex clonal and plasmid epidemiology in the first outbreak of Enterobacteriaceae infection involving VIM-1 metallo-beta-lactamase in Spain: toward endemicity?
abstract: BACKGROUND
  We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain).
  
  
  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.
authors.affiliation: Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Tato
authors.forename: T M
authors.initials: TM
authors.lastname: Coque
authors.forename: P
authors.initials: P
authors.lastname: Ruíz-Garbajosa
authors.forename: V
authors.initials: V
authors.lastname: Pintado
authors.forename: J
authors.initials: J
authors.lastname: Cobo
authors.forename: H S
authors.initials: HS
authors.lastname: Sader
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: F
authors.initials: F
authors.lastname: Baquero
authors.forename: R
authors.initials: R
authors.lastname: Cantón
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003001:Cloning, Molecular; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000201:enzymology / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics; D013030:Spain / Q000453:epidemiology; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases