Complex Clonal And Plasmid Epidemiology In The First Outbreak Of Enterobacteriaceae Infection Involving Vim-1 Metallo-Beta-Lactamase In Spain: Toward Endemicity?

Background. We report the emergence and spread of metallo-beta-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 >18 mu g/ 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.