Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital

Clin Infect Dis. 2008 Mar 15;46(6):847-54. doi: 10.1086/528719.


Background: The dissemination of acquired metallo-beta-lactamases (MBLs) in members of the family Enterobacteriaceae is regarded as an emerging clinical threat. The clinical characteristics and outcomes of 17 cases of infection due to MBL-producing isolates were analyzed.

Methods: During a 3-year period, medical records for all patients with confirmed infection due to an MBL-producing strain belonging to the Enterobacteriaceae family were retrospectively analyzed. We screened for MBL production with the imipenem-ethylenediaminetetraacetic acid disk synergy test, and results were confirmed by polymerase chain reaction. Genetic relatedness between isolates was evaluated by repetitive extragenic palindromic polymerase chain reaction.

Results: Fourteen cases of bacteremia and 3 cases of ventilator-associated pneumonia due to an MBL-producing isolate were studied. Most of the patients had previously been colonized with an MBL-producing organism, and almost 60% had been exposed to carbapenems before infection. The isolated pathogens (Klebsiella pneumoniae, 14 cases; and Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes, 1 case each) exhibited variable minimum inhibitor concentrations of carbapenems (1 to >32 microg/mL) and resistance to most other beta-lactams. Tigecycline was active against all isolates, whereas colistin and gentamicin were active against 88% of them. Molecular studies confirmed the presence of a gene belonging to bla(VIM-1) cluster in all isolates. Among the 12 K. pneumoniae isolates, which were subjected to molecular typing, 11 distinct clones were identified. Five cases ( approximately 30%) occurred in patients who were already receiving carbapenem-containing treatment, and carbapenem treatment was considered to have failed. Twelve cases were treated with a colistin-containing regimen. The attributable mortality rate was 18.8%.

Conclusions: MBL-producing Enterobacteriaceae can cause severe, often fatal infection in severely ill patients, irrespective of the MIC of carbapenems. Colonization with an MBL-producer is a preceding event, highlighting the importance of surveillance. Both infection control practices and antibiotic policies should be intensified to contain the spread of these problematic bacteria.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteremia / microbiology
  • Bacteremia / mortality
  • Bacteremia / physiopathology
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / pathogenicity*
  • Enterobacteriaceae Infections* / microbiology
  • Enterobacteriaceae Infections* / mortality
  • Enterobacteriaceae Infections* / physiopathology
  • Female
  • Greece / epidemiology
  • Hospitals, University
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / mortality
  • Klebsiella Infections / physiopathology
  • Klebsiella pneumoniae
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / mortality
  • Pneumonia, Bacterial / physiopathology
  • Polymerase Chain Reaction
  • beta-Lactam Resistance*
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics


  • VIM-1 metallo-beta-lactamase
  • beta-Lactamases