title: Synbiotics and probiotics in the critically ill after the PROPATRIA trial.
abstract: OBJECTIVE
  Recent clinical trials have furthered our understanding of the role of probiotic and synbiotic therapy across a variety of diverse diseases including antibiotic-associated diarrhea, Clostridium difficile associated diarrhea, acute pancreatitis, ventilator-associated pneumonia, and sepsis among others. Although each of these conditions has implications for critically ill patients, relatively few studies have specifically studied this vulnerable population.
  
  
  RESULTS
  One recent clinical trial studying probiotics in severe pancreatitis (the PROPATRIA trial) found an unexpected increase in mortality in probiotic-treated patients. These results stimulated an immediate, extensive, and badly overdue discussion focused on the need for improved safety monitoring during the execution of all clinical trials using probiotics. However, issues with the design, execution, and analysis of PROPATRIA ultimately created more questions than it answered.
  
  
  CONCLUSIONS
  Regardless of technical issues with the study, the increased mortality seen with probiotics cannot be ignored. As a result, various regulatory agencies have clarified their stance on the safety of probiotic research and the legacy of PROPATRIA is increasingly stringent regulation of this fledgling niche.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Nebraska, USA. lmorrow@creighton.edu
authors.forename: Lee E
authors.initials: LE
authors.lastname: Morrow
authors.forename: Vijaya
authors.initials: V
authors.lastname: Gogineni
authors.forename: Mark A
authors.initials: MA
authors.lastname: Malesker
mesh_terms: D000208:Acute Disease; D016360:Clostridioides difficile / Q000254:growth & development / Q000472:pathogenicity; D016638:Critical Illness / Q000628:therapy*; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy; D006801:Humans; D015201:Meta-Analysis as Topic; D010195:Pancreatitis / Q000628:therapy; D053717:Pneumonia, Ventilator-Associated / Q000628:therapy; D019936:Probiotics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D058616:Synbiotics; D016896:Treatment Outcome