title: Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital.
abstract: 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.
authors.affiliation: Fourth Department of Internal Medicine, Athens University Medical School, University General Hospital Attikon, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Souli
authors.forename: Flora V
authors.initials: FV
authors.lastname: Kontopidou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Papadomichelakis
authors.forename: Irene
authors.initials: I
authors.lastname: Galani
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D005260:Female; D006115:Greece / Q000453:epidemiology; D006785:Hospitals, University; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D007711:Klebsiella pneumoniae; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
chemical_list: C417264:VIM-1 metallo-beta-lactamase; D001618:beta-Lactamases