title: Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence.
abstract: BACKGROUND
  Accurate tracking of Clostridium difficile transmission within healthcare settings is key to its containment but is hindered by the lack of discriminatory power of standard genotyping methods. We describe a whole-genome phylogenetic-based method to track the transmission of individual clones in infected hospital patients from the epidemic C. difficile 027/ST1 lineage, and to distinguish between the 2 causes of recurrent disease, relapse (same strain), or reinfection (different strain).
  
  
  METHODS
  We monitored patients with C. difficile infection in a UK hospital over a 2-year period. We performed whole-genome sequencing and phylogenetic analysis of 108 strains isolated from symptomatic patients. High-resolution phylogeny was integrated with in-hospital transfers and contact data to create an infection network linking individual patients and specific hospital wards.
  
  
  RESULTS
  Epidemic C. difficile 027/ST1 caused the majority of infections during our sampling period. Integration of whole-genome single nucleotide polymorphism (SNP) phylogenetic analysis, which accurately discriminated between 27 distinct SNP genotypes, with patient movement and contact data identified 32 plausible transmission events, including ward-based contamination (66%) or direct donor-recipient contact (34%). Highly contagious donors were identified who contributed to the persistence of clones within distinct hospital wards and the spread of clones between wards, especially in areas of intense turnover. Recurrent cases were identified between 4 and 26 weeks, highlighting the limitation of the standard <8-week cutoff used for patient diagnosis and management.
  
  
  CONCLUSIONS
  Genome-based infection tracking to monitor the persistence and spread of C. difficile within healthcare facilities could inform infection control and patient management.
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Nitin
authors.initials: N
authors.lastname: Kumar
authors.affiliation: University of Liverpool.
authors.forename: Fabio
authors.initials: F
authors.lastname: Miyajima
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Paul
authors.initials: P
authors.lastname: Roberts
authors.affiliation: University of Liverpool.
authors.forename: Andrew
authors.initials: A
authors.lastname: Swale
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Louise
authors.initials: L
authors.lastname: Ellison
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.affiliation: Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Smith
authors.affiliation: Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Molyneux
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.affiliation: London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.affiliation: University of Liverpool.
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.affiliation: WellcomeTrust Sanger Institute, Hinxton.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
mesh_terms: D000328:Adult; D016360:Clostridioides difficile / Q000235:genetics* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000453:epidemiology* / Q000382:microbiology / Q000517:prevention & control / Q000635:transmission*; D003428:Cross Infection / Q000382:microbiology / Q000517:prevention & control / Q000635:transmission*; D004196:Disease Outbreaks / Q000517:prevention & control; D005260:Female; D016680:Genome, Bacterial; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D021521:Ribotyping; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
keywords: C. difficile 027/ST1; highly contagious individuals; recurrence; ward-based transmission; whole-genome sequencing