title: Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial.
abstract: BACKGROUND
  Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs.
  
  
  METHODS
  We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12-15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638.
  
  
  RESULTS
  Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954-0·999) for phase 2 and 1·015 (0·998-1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676-1·348) for phase 2 and 0·634 (0·349-1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890-0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06).
  
  
  CONCLUSIONS
  Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing.
  
  
  BACKGROUND
  European Commission.
authors.affiliation: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: lderde@umcutrecht.nl.
authors.forename: Lennie P G
authors.initials: LPG
authors.lastname: Derde
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Ben S
authors.initials: BS
authors.lastname: Cooper
authors.affiliation: Department of Medical Microbiology, Vaccine & Infectious Disease Institute, Antwerp University, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Department of Medical Microbiology, Vaccine & Infectious Disease Institute, Antwerp University, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Malhotra-Kumar
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Rob J L
authors.initials: RJL
authors.lastname: Willems
authors.affiliation: Department of Molecular Microbiology, National Medicines Institute, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Gniadkowski
authors.affiliation: Division of Microbiology and Infection Prevention, National Medicines Institute, Warsaw, Poland.
authors.forename: Waleria
authors.initials: W
authors.lastname: Hryniewicz
authors.affiliation: Department of Molecular Microbiology, National Medicines Institute, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Empel
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Mirjam J D
authors.initials: MJD
authors.lastname: Dautzenberg
authors.affiliation: Service de Réanimation Médicale, Hôpital Raymond Poincaré, Garches, France.
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
authors.affiliation: Polyvalent Intensive Care Unit, Central Hospital of Porto, Porto, Portugal.
authors.forename: Irene
authors.initials: I
authors.lastname: Aragão
authors.affiliation: Infection Control Unit, Groupe Hospitalier Paris-Saint Joseph, Paris, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Chalfine
authors.affiliation: Department of Infection Control, Paul Stradins University Hospital, Riga, Latvia.
authors.forename: Uga
authors.initials: U
authors.lastname: Dumpis
authors.affiliation: ICU and Emergency Department, Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Esteves
authors.affiliation: 4th Department of Internal Medicine, Athens University Medical School, Attikon General Hospital, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
authors.affiliation: Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Igor
authors.initials: I
authors.lastname: Muzlovic
authors.affiliation: Shock and Trauma Unit, Intensive Care Unit, Azienda Ospedaliera S Camillo Forlanini, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nardi
authors.affiliation: Infectious Diseases Unit, Laikon General Hospital, University of Athens, Athens, Greece.
authors.forename: George L
authors.initials: GL
authors.lastname: Petrikkos
authors.affiliation: Laboratory for Respiratory Microbiology, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.
authors.forename: Viktorija
authors.initials: V
authors.lastname: Tomic
authors.affiliation: Pneumology Department, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Ciber de Enfermedades Respiratorias, University of Barcelona, Barcelona, Spain.
authors.forename: Antonio Torres
authors.initials: AT
authors.lastname: Martí
authors.affiliation: Intensive Care Unit, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
authors.forename: Pascal
authors.initials: P
authors.lastname: Stammet
authors.affiliation: Service de réanimation médicale and INSERM U657, Institut Pasteur, APHP GH Henri Mondor, Université Paris Est-Créteil, Creteil, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Marc J M
authors.initials: MJM
authors.lastname: Bonten
mesh_terms: D000368:Aged; D001424:Bacterial Infections / Q000175:diagnosis / Q000517:prevention & control* / Q000635:transmission; D002353:Carrier State / Q000175:diagnosis*; D002710:Chlorhexidine / Q000627:therapeutic use*; D003428:Cross Infection / Q000517:prevention & control* / Q000635:transmission; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004202:Disinfectants / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000302:isolation & purification; D016983:Enterococcus / Q000302:isolation & purification; D005260:Female; D006235:Hand Disinfection / Q000379:methods; D006801:Humans; D015994:Incidence; D017053:Infection Control / Q000379:methods; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D013211:Staphylococcus aureus / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D004202:Disinfectants; D002710:Chlorhexidine