title: Multiple hospital outbreaks of vanA Enterococcus faecium in Denmark, 2012-13, investigated by WGS, MLST and PFGE.
abstract: OBJECTIVE
  In Denmark, the incidence of vancomycin-resistant Enterococcus faecium (VREfm) has increased since 2012. The aim of this study was to investigate the epidemiology and clonal relatedness of VREfm isolates in Danish hospitals in 2012-13 using WGS. The second aim was to evaluate if WGS-based typing could replace PFGE for typing of VREfm.
  
  
  METHODS
  A population-based study was conducted including all VREfm isolates submitted for national surveillance from January 2012 to April 2013. All isolates were investigated by WGS, MLST and PFGE.
  
  
  RESULTS
  One-hundred and thirty-two isolates were included. The majority of the isolates were from clinical samples (77%). Gastroenterology/abdominal surgery (29%) and ICUs (29%) were the predominant departments with VREfm. Genomics revealed a polyclonal structure of the VREfm outbreak. Seven subgroups of 3-44 genetically closely related isolates (separated by <17 SNPs) were identified using WGS. Direct or indirect transmission of VREfm between patients and intra- and inter-regional spreading clones was observed. We identified 10 STs. PFGE identified four major clusters (13-43 isolates) and seven minor clusters (two to three isolates). The results from the typing methods were highly concordant. However, WGS-based typing had the highest discriminatory power.
  
  
  CONCLUSIONS
  This study emphasizes the importance of infection control measures to limit transmission of VREfm between patients. However, the diversity of the VREfm isolates points to the fact that other important factors may also affect the VREfm increase in Denmark. Finally, WGS is suitable for typing of VREfm and has replaced PFGE for typing of VREfm in Denmark.
authors.affiliation: Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark mette.pinholt@regionh.dk.
authors.forename: Mette
authors.initials: M
authors.lastname: Pinholt
authors.affiliation: The Danish National Biobank, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Hanna
authors.initials: H
authors.lastname: Larner-Svensson
authors.affiliation: Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Littauer
authors.affiliation: Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus E
authors.initials: CE
authors.lastname: Moser
authors.affiliation: Department of Clinical Microbiology, Herlev University Hospital, Herlev, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Lemming
authors.affiliation: Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Tove
authors.initials: T
authors.lastname: Ejlertsen
authors.affiliation: Department of Clinical Microbiology, Regional Hospital Central Jutland, Herning-Viborg, Denmark.
authors.forename: Turid S
authors.initials: TS
authors.lastname: Søndergaard
authors.affiliation: Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Holzknecht
authors.affiliation: Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark.
authors.forename: Ulrik S
authors.initials: US
authors.lastname: Justesen
authors.affiliation: Department of Clinical Microbiology, Esbjerg Hospital, Esbjerg, Denmark.
authors.forename: Esad
authors.initials: E
authors.lastname: Dzajic
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Olsen
authors.affiliation: Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
authors.forename: Peder
authors.initials: P
authors.lastname: Worning
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Anette M
authors.initials: AM
authors.lastname: Hammerum
authors.affiliation: Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Westh
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Jakobsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000235:genetics*; D019729:Carbon-Oxygen Ligases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D004196:Disease Outbreaks; D016984:Enterococcus faecium / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D005838:Genotype; D016908:Gram-Positive Bacterial Infections / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology / Q000379:methods; D058889:Molecular Typing / Q000379:methods*; D065507:Vancomycin-Resistant Enterococci / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; C071437:VanA ligase, Bacteria; D019729:Carbon-Oxygen Ligases
keywords: resistance; surveillance; typing methods