title: Characterization of carbapenemase-producing Enterobacteriaceae in the West Midlands region of England: 2007-14.
abstract: Carbapenemase-producing Enterobacteriaceae (CPE) have been increasingly reported in the UK since 2003. We analysed patient and isolate data for CPE confirmed by the national reference laboratory from laboratories in the West Midlands region from November 2007 to December 2014.
  
  
  
  MICs were determined by BSAC agar dilution methodology and isolates exhibiting resistance to one or more carbapenems were screened for carbapenemase genes by PCR. Plasmid analyses were performed after electro-transformation of carbapenemase-encoding plasmids. WGS was performed on both transformants and clinical isolates. Patient data provided by the sending laboratories were reviewed.
  
  
  
  During the study period, CPE ( n  = 139) were submitted from 13 laboratories in the West Midlands region, originating from 108 patients and including one environmental isolate. CPE submissions increased significantly from 2009 onwards. Isolates were predominantly Klebsiella pneumoniae (89/139) obtained from inpatients. WGS was performed on all clinical isolates and transformants. After deduplication 119 isolates and 96 transformants remained for analysis. Within these, four families of carbapenemase genes were identified: bla NDM (69/119), bla KPC (26/119), bla OXA-48-like (16/119) and bla VIM (7/119); one isolate carried both bla NDM and bla OXA-48-like . Isolates represented diverse STs and plasmid replicon types. Plasmid analyses identified plasmids of different replicon types encoding bla KPC , bla NDM and bla OXA-48-like genes, found across several species and STs.
  
  
  
  CPE have been reported increasingly in the West Midlands region over a 7 year period. bla NDM , bla KPC and bla OXA-48-like were the dominant carbapenemase genes and were found in a range of diverse genomic/plasmid environments, highlighting their ability to mobilize across different plasmids, often impeding the detection of outbreaks.
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Findlay
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Hopkins
authors.affiliation: PHE Public Health Laboratory Birmingham, Heart of England NHS Foundation Trust, Birmingham B9 5SS, UK.
authors.forename: Adela
authors.initials: A
authors.lastname: Alvarez-Buylla
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Daniéle
authors.initials: D
authors.lastname: Meunier
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Nazim
authors.initials: N
authors.lastname: Mustafa
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Hill
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Pike
authors.affiliation: PHE Public Health Laboratory Birmingham, Heart of England NHS Foundation Trust, Birmingham B9 5SS, UK.
authors.forename: Li-Xu
authors.initials: LX
authors.lastname: McCrae
authors.affiliation: PHE Public Health Laboratory Birmingham, Heart of England NHS Foundation Trust, Birmingham B9 5SS, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Hawkey
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Woodford
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D004739:England / Q000453:epidemiology; D004755:Enterobacteriaceae / Q000145:classification* / Q000201:enzymology / Q000302:isolation & purification*; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010957:Plasmids / Q000032:analysis; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014169:Transformation, Bacterial; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase