title: Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial.
abstract: Probiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU).
  
  
  
  In a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 10(10) colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality.
  
  
  
  Overall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7-18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14-44 days); 23 patients (15.3 %) died in the ICU.
  
  
  
  The PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients.
  
  
  
  Clinicaltrials.gov NCT01782755 . Registered on 29 January 2013.
authors.affiliation: Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada. debcook@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. debcook@mcmaster.ca.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.affiliation: Public Health Ontario, Toronto, ON, Canada.|St. Joseph's Health Center, Toronto, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Jennie
authors.initials: J
authors.lastname: Johnstone
authors.affiliation: Department of Surgery, University of Toronto, Toronto, ON, Canada.|Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.affiliation: Research Center of the CHU de Québec - Population Health and Optimal Health Practices Research Unit, Université Laval, Quebec City, QC, Canada.|Department of Medicine, Université Laval, Quebec City, QC, Canada.|Department of Anesthesiology and Critical Care, Université Laval, Quebec City, QC, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Lauzier
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada.|Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Division of Critical Care Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada.|Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Dodek
authors.affiliation: Division of Critical Care, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: McIntyre
authors.affiliation: Division of Critical Care, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Joe
authors.initials: J
authors.lastname: Pagliarello
authors.affiliation: Division of Critical Care Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Henderson
authors.affiliation: Department of Critical Care Medicine, Mercy Hospital, St Louis, MO, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cartin-Ceba
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada.|Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
authors.forename: Eyal
authors.initials: E
authors.lastname: Golan
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada.|Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Herridge
authors.affiliation: Department of Anesthesia & Critical Care, Vancouver Island Health Authority, Victoria, BC, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Wood
authors.affiliation: Department of Anesthesia & Critical Care, Vancouver Island Health Authority, Victoria, BC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ovakim
authors.affiliation: Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada.
authors.forename: Tim
authors.initials: T
authors.lastname: Karachi
authors.affiliation: Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Dawn M E
authors.initials: DM
authors.lastname: Bowdish
authors.affiliation: Biochemistry and Biomedical Sciences Department, McMaster University, Hamilton, ON, Canada.
authors.forename: Daphnee
authors.initials: D
authors.lastname: Lamarche
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Verschoor
authors.affiliation: Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada.
authors.forename: Erick H
authors.initials: EH
authors.lastname: Duan
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.affiliation: King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Arabi
authors.affiliation: Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
mesh_terms: D000328:Adult; D000368:Aged; D002170:Canada; D005240:Feasibility Studies; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007442:Intubation, Intratracheal / Q000009:adverse effects* / Q000401:mortality; D052201:Lacticaseibacillus rhamnosus / Q000254:growth & development*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D019936:Probiotics / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D013997:Time Factors; D014132:Trachea / Q000382:microbiology*; D016896:Treatment Outcome; D014481:United States
keywords: Critically ill; Infection; Intensive care; Probiotics