title: Genomic epidemiology of a protracted hospital outbreak caused by multidrug-resistant Acinetobacter baumannii in Birmingham, England.
abstract: BACKGROUND
  Multidrug-resistant Acinetobacter baumannii commonly causes hospital outbreaks. However, within an outbreak, it can be difficult to identify the routes of cross-infection rapidly and accurately enough to inform infection control. Here, we describe a protracted hospital outbreak of multidrug-resistant A. baumannii, in which whole-genome sequencing (WGS) was used to obtain a high-resolution view of the relationships between isolates.
  
  
  METHODS
  To delineate and investigate the outbreak, we attempted to genome-sequence 114 isolates that had been assigned to the A. baumannii complex by the Vitek2 system and obtained informative draft genome sequences from 102 of them. Genomes were mapped against an outbreak reference sequence to identify single nucleotide variants (SNVs).
  
  
  RESULTS
  We found that the pulsotype 27 outbreak strain was distinct from all other genome-sequenced strains. Seventy-four isolates from 49 patients could be assigned to the pulsotype 27 outbreak on the basis of genomic similarity, while WGS allowed 18 isolates to be ruled out of the outbreak. Among the pulsotype 27 outbreak isolates, we identified 31 SNVs and seven major genotypic clusters. In two patients, we documented within-host diversity, including mixtures of unrelated strains and within-strain clouds of SNV diversity. By combining WGS and epidemiological data, we reconstructed potential transmission events that linked all but 10 of the patients and confirmed links between clinical and environmental isolates. Identification of a contaminated bed and a burns theatre as sources of transmission led to enhanced environmental decontamination procedures.
  
  
  CONCLUSIONS
  WGS is now poised to make an impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant timeframe and allowing infection control teams to track, and even prevent, the spread of drug-resistant hospital pathogens.
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT UK.
authors.forename: Mihail R
authors.initials: MR
authors.lastname: Halachev
authors.affiliation: Division of Microbiology and Infection, Warwick Medical School, University of Warwick, Warwick, CV4 7AL UK.
authors.forename: Jacqueline Z-M
authors.initials: JZ
authors.lastname: Chan
authors.affiliation: Division of Microbiology and Infection, Warwick Medical School, University of Warwick, Warwick, CV4 7AL UK.
authors.forename: Chrystala I
authors.initials: CI
authors.lastname: Constantinidou
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Medical Centre, Birmingham, B15 2TH UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cumley
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Medical Centre, Birmingham, B15 2TH UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Bradley
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Medical Centre, Birmingham, B15 2TH UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith-Banks
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Medical Centre, Birmingham, B15 2TH UK.
authors.forename: Beryl
authors.initials: B
authors.lastname: Oppenheim
authors.affiliation: Division of Microbiology and Infection, Warwick Medical School, University of Warwick, Warwick, CV4 7AL UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen