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

Abstract
Background. We report the emergence and spread of metallo-β-lactamases (MBLs) among enterobacterial isolates at Ramon 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, ⩽1 to >8 µg/mL), as were aminoglycosides and ciprofloxacin. The blaVIM-1 MBL gene was present in all isolates; in addition, the blaSHV-12 extended-spectrum β-lactamase gene was detected in K. pneumoniae and E. coli isolates. The blaVIM-1 gene was detected within a 4.0-kb class 1 integron (blaVIM-1-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (blaVIM-1-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The blaVIM-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 blaVIM-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.