title: Safety of probiotics in patients receiving nutritional support: a systematic review of case reports, randomized controlled trials, and nonrandomized trials.
abstract: BACKGROUND
  Probiotics are increasingly used in patients receiving nutritional support; however, some case reports and trials have questioned their safety in such patients.
  
  
  OBJECTIVE
  The objective was to investigate the safety of probiotics in patients receiving nutritional support through a systematic review of case reports, randomized controlled trials (RCTs), and nonrandomized trials.
  
  
  METHODS
  The systematic review followed Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Six electronic databases were searched, a hand search of conference proceedings and reference lists was performed, and experts were contacted. Case reports, RCTs, and nonrandomized trials of probiotic use in patients also receiving enteral or parenteral nutrition were included in the review. Two reviewers independently screened the relevant articles and extracted the data.
  
  
  RESULTS
  In total, 1966 articles were identified, of which 72 fulfilled the inclusion criteria. There were 20 case reports of adverse events in 32 patients, all of which were infections due to Lactobacillus rhamnosus GG or Saccharomyces boulardii; the risk factors included central venous catheters and disorders associated with increased bacterial translocation. There were 52 articles reporting 53 trials in which 4131 patients received probiotics. Most trials showed either no effect or a positive effect on outcomes related to safety (eg, mortality and infections). Only 3 trials showed increased complications, which were largely noninfectious in nature and in specific patient groups (eg, transplant and pancreatitis). In 2 of these trials, the probiotic was administered through a postpyloric tube.
  
  
  CONCLUSIONS
  Many probiotics have been used safely in patients receiving nutritional support, although some probiotic products (strains or combinations) have been shown to increase the risk of complications in specific patient groups.
authors.affiliation: King's College, London, UK. kevin.whelan@kcl.ac.uk
authors.forename: Kevin
authors.initials: K
authors.lastname: Whelan
authors.forename: Clio E
authors.initials: CE
authors.lastname: Myers
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007239:Infections / Q000453:epidemiology*; D052201:Lacticaseibacillus rhamnosus; D018529:Nutritional Support / Q000379:methods; D019936:Probiotics / Q000009:adverse effects*; D012307:Risk Factors; D012440:Saccharomyces