title: Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing.
abstract: Health-care workers have been implicated in nosocomial outbreaks of Staphylococcus aureus, but the dearth of evidence from non-outbreak situations means that routine health-care worker screening and S aureus eradication are controversial. We aimed to determine how often S aureus is transmitted from health-care workers or the environment to patients in an intensive care unit (ICU) and a high-dependency unit (HDU) where standard infection control measures were in place.
  
  
  
  In this longitudinal cohort study, we systematically sampled health-care workers, the environment, and patients over 14 months at the ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs were taken from health-care workers every 4 weeks, bed spaces were sampled monthly, and screening swabs were obtained from patients at admission to the ICU or HDU, weekly thereafter, and at discharge. Isolates were cultured and their whole genome sequenced, and we used the threshold of 40 single-nucleotide variants (SNVs) or fewer to define subtypes and infer recent transmission.
  
  
  
  Between Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care workers, 40 environmental locations, and 1854 patients; 1819 isolates were sequenced. Median nasal carriage rate of S aureus in health-care workers at 4-weekly timepoints was 36·9% (IQR 35·7-37·3), and 115 (58%) health-care workers had S aureus detected at least once during the study. S aureus was identified in 8-50% of environmental samples. 605 genetically distinct subtypes were identified (median SNV difference 273, IQR 162-399) at a rate of 38 (IQR 34-42) per 4-weekly cycle. Only 25 instances of transmission to patients (seven from health-care workers, two from the environment, and 16 from other patients) were detected.
  
  
  
  In the presence of standard infection control measures, health-care workers were infrequently sources of transmission to patients. S aureus epidemiology in the ICU and HDU is characterised by continuous ingress of distinct subtypes rather than transmission of genetically related strains.
  
  
  
  UK Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, UK National Institute for Health Research, and Public Health England.
authors.affiliation: Department of Microbiology and Infection, Royal Sussex County Hospital, Brighton, UK. Electronic address: jrprice@doctors.org.uk.
authors.forename: James R
authors.initials: JR
authors.lastname: Price
authors.affiliation: Department of Microbiology and Infection, Royal Sussex County Hospital, Brighton, UK; Public Health England, Royal Sussex County Hospital, Brighton, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cole
authors.affiliation: Department of Microbiology and Infection, Royal Sussex County Hospital, Brighton, UK; Public Health England, Royal Sussex County Hospital, Brighton, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bexley
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kostiou
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Eyre
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK.
authors.forename: Tanya
authors.initials: T
authors.lastname: Golubchik
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK; Public Health England, London, UK.
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.affiliation: Nuffield Department of Clinical Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
authors.forename: Timothy E A
authors.initials: TEA
authors.lastname: Peto
authors.affiliation: Department of Microbiology and Infection, Royal Sussex County Hospital, Brighton, UK; Division of Medicine, Brighton and Sussex Medical School, Falmer, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Llewelyn
authors.affiliation: Department of Microbiology and Infection, Royal Sussex County Hospital, Brighton, UK; Public Health England, Royal Sussex County Hospital, Brighton, UK.
authors.forename: John
authors.initials: J
authors.lastname: Paul
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003428:Cross Infection / Q000382:microbiology / Q000517:prevention & control / Q000635:transmission*; D004739:England; D004777:Environment; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D017053:Infection Control / Q000379:methods; D007362:Intensive Care Units; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000382:microbiology / Q000635:transmission*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification