title: First nosocomial outbreak of vancomycin-resistant Enterococcus faecium expressing a VanD-like phenotype associated with a vanA genotype.
abstract: Although enterococci expressing acquired vancomycin resistance phenotype have been reported increasingly worldwide, they have been rarely reported in France. From August to December 2004 we faced an outbreak of vancomycin-resistant Enterococcus faecium (VRE) isolates in the nephrology department at Bicêtre Hospital (K.-Bicêtre, France). The expression of the glycopeptide resistance varied among the 26 VRE isolates, with vancomycin MICs ranging from 12 to >256 microg/ml, whereas teicoplanin MICs ranged from 4 to 48 microg/ml. However, several strains appeared to be susceptible to glycopeptides according to disk diffusion testing and expressed resistance only after subculture with glycopeptides. In addition, a heterogeneous expression of glycopeptide resistance was also observed. This so-called VanD-like phenotype of resistance (low-level resistance to vancomycin and mostly susceptibility to teicoplanin) was surprisingly associated with a vanA gene. Plasmid extraction and mating-out experiments indicated that the vanA gene was located on a 200-kb self-transferable plasmid. Pulsed-field gel electrophoresis identified mostly dissemination of a single clone, whereas diffusion of the VanA-positive plasmid in different genomic backgrounds had also occurred. The vanA gene was part of a vanA-type operon for expression of resistance located on a Tn1546-like transposon. Sequencing of this transposon identified insertion of insertion sequence IS16 in the vanY gene that encodes a d,d-carboxypeptidase that might explain in part the peculiar VanD-type phenotype of resistance. This report is the first description of a VRE outbreak in France and underlines the difficulty in detecting this organism due to variability on the expression of the glycopeptide resistance trait, if any.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Université Paris IX, 78 rue du Général Leclerc 94275 Le Kremlin-Bicêtre Cedex, France. thierry.naas@bct.ap-hop-paris.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Naas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fortineau
authors.forename: Renaud
authors.initials: R
authors.lastname: Snanoudj
authors.forename: Colette
authors.initials: C
authors.lastname: Spicq
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics*; D015373:Bacterial Typing Techniques; D019729:Carbon-Oxygen Ligases / Q000235:genetics*; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology*; D004251:DNA Transposable Elements; D004196:Disease Outbreaks; D016984:Enterococcus faecium / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010453:Peptide Synthases / Q000032:analysis*; D010641:Phenotype; D020713:Vancomycin Resistance
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C071437:VanA ligase, Bacteria; D019729:Carbon-Oxygen Ligases; D010453:Peptide Synthases; C122181:VanD protein, Enterococcus faecium