title: Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis.
abstract: BACKGROUND
  Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness.
  
  
  METHODS
  Computerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes.
  
  
  RESULTS
  Thirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I (2) = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I (2) = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists.
  
  
  CONCLUSIONS
  Probiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.
authors.affiliation: Department of Critical Care, Intensive Care Unit, Hospital de Clínicas (University Hospital), Faculty of Medicine, Universidad de la República (UdelaR), Italia Av, 14th Floor, 11.600, Montevideo, Uruguay.
authors.forename: William
authors.initials: W
authors.lastname: Manzanares
authors.affiliation: Clinical Evaluation Research Unit. Angada 4, Kingston General Hospital, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada.
authors.forename: Margot
authors.initials: M
authors.lastname: Lemieux
authors.affiliation: Département de Anesthésie et de Réanimation, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke-Hôpital Fleurimont, Pièce 3610 3001, 12e Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Pascal L
authors.initials: PL
authors.lastname: Langlois
authors.affiliation: Department of Anesthesiology and Pediatrics (Nutrition Section), University of Colorado, School of Medicine, 12700 E. 19th Ave., RC2 P15-7120, Box 8602, Aurora, CO, 80045, USA. Paul.Wischmeyer@ucdenver.edu.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wischmeyer
mesh_terms: D001424:Bacterial Infections / Q000517:prevention & control*; D016638:Critical Illness; D003428:Cross Infection / Q000517:prevention & control*; D006801:Humans; D053717:Pneumonia, Ventilator-Associated / Q000517:prevention & control; D019936:Probiotics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D058616:Synbiotics; D016896:Treatment Outcome
keywords: Critical care; Infections; Probiotics; Synbiotics; Systematic review; Ventilator-associated pneumonia