title: Characterisation of Clostridium difficile hospital ward-based transmission using extensive epidemiological data and molecular typing.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea and is endemic in hospitals, hindering the identification of sources and routes of transmission based on shared time and space alone. This may compromise rational control despite costly prevention strategies. This study aimed to investigate ward-based transmission of C. difficile, by subdividing outbreaks into distinct lineages defined by multi-locus sequence typing (MLST).
  
  
  RESULTS
  All C. difficile toxin enzyme-immunoassay-positive and culture-positive samples over 2.5 y from a geographically defined population of ~600,000 persons underwent MLST. Sequence types (STs) were combined with admission and ward movement data from an integrated comprehensive healthcare system incorporating three hospitals (1,700 beds) providing all acute care for the defined geographical population. Networks of cases and potential transmission events were constructed for each ST. Potential infection sources for each case and transmission timescales were defined by prior ward-based contact with other cases sharing the same ST. From 1 September 2007 to 31 March 2010, there were means of 102 tests and 9.4 CDIs per 10,000 overnight stays in inpatients, and 238 tests and 15.7 CDIs per month in outpatients/primary care. In total, 1,276 C. difficile isolates of 69 STs were studied. From MLST, no more than 25% of cases could be linked to a potential ward-based inpatient source, ranging from 37% in renal/transplant, 29% in haematology/oncology, and 28% in acute/elderly medicine to 6% in specialist surgery. Most of the putative transmissions identified occurred shortly (≤ 1 wk) after the onset of symptoms (141/218, 65%), with few >8 wk (21/218, 10%). Most incubation periods were ≤ 4 wk (132/218, 61%), with few >12 wk (28/218, 13%). Allowing for persistent ward contamination following ward discharge of a CDI case did not increase the proportion of linked cases after allowing for random meeting of matched controls.
  
  
  CONCLUSIONS
  In an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic enzyme-immunoassay-positive patients cannot account for most new CDI cases.
authors.affiliation: National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom. asw@ctu.mrc.ac.uk
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.forename: David W
authors.initials: DW
authors.lastname: Eyre
authors.forename: David H
authors.initials: DH
authors.lastname: Wyllie
authors.forename: Kate E
authors.initials: KE
authors.lastname: Dingle
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: Harding
authors.forename: Lily
authors.initials: L
authors.lastname: O'Connor
authors.forename: David
authors.initials: D
authors.lastname: Griffiths
authors.forename: Ali
authors.initials: A
authors.lastname: Vaughan
authors.forename: John
authors.initials: J
authors.lastname: Finney
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wilcox
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.forename: Tim E A
authors.initials: TE
authors.lastname: Peto
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects; D001483:Base Sequence; D016360:Clostridioides difficile / Q000235:genetics* / Q000302:isolation & purification; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D003967:Diarrhea / Q000209:etiology* / Q000382:microbiology; D019353:Endemic Diseases; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006757:Hospital Units; D006760:Hospitalization; D006801:Humans; D017053:Infection Control; D058885:Multilocus Sequence Typing / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents