title: Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients.
abstract: BACKGROUND
  Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized.
  
  
  METHODS
  We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events.
  
  
  RESULTS
  Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%-8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%-51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization.
  
  
  CONCLUSIONS
  These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ~50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute.|Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Gorrie
authors.affiliation: Microbiology Unit, Alfred Health, Melbourne, Victoria, Australia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Mirceta
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Wick
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute.
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
authors.affiliation: Infectious Diseases Clinical Research Unit.
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Pratt
authors.affiliation: Infectious Diseases Clinical Research Unit.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Garlick
authors.affiliation: Infectious Diseases Clinical Research Unit.
authors.forename: Kerri M
authors.initials: KM
authors.lastname: Watson
authors.affiliation: Intensive Care Unit, The Alfred Hospital.|Australian and New Zealand Intensive Care - Research Centre, School of Public Health and Preventive Medicine, Monash University.
authors.forename: David V
authors.initials: DV
authors.lastname: Pilcher
authors.affiliation: Intensive Care Unit, The Alfred Hospital.|Australian and New Zealand Intensive Care - Research Centre, School of Public Health and Preventive Medicine, Monash University.
authors.forename: Steve A
authors.initials: SA
authors.lastname: McGloughlin
authors.affiliation: Microbiology Unit & Department of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Denis W
authors.initials: DW
authors.lastname: Spelman
authors.affiliation: Microbiology Unit & Department of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Adam W J
authors.initials: AWJ
authors.lastname: Jenney
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002353:Carrier State / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D015331:Cohort Studies; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D014644:Genetic Variation; D006801:Humans; D007362:Intensive Care Units; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000635:transmission; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010614:Pharynx / Q000382:microbiology; D011446:Prospective Studies; D012007:Rectum / Q000382:microbiology; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents
keywords: Klebsiella pneumoniae; gastrointestinal colonization; genomic epidemiology; hospital acquired infection; intensive care