title: A reassessment of the PROPATRIA study and its implications for probiotic therapy.
abstract: The PROPATRIA (Probiotics in Pancreatitis Trial) study was a multicenter, double-blind, placebo-controlled clinical trial that aimed to reduce infectious complications in patients with predicted severe acute pancreatitis by the enteral use of a multispecies probiotic preparation. An unprecedented 24 of 152 patients (16%) in the group receiving probiotics died versus 9 of 144 (6%) in the placebo group. This high mortality rate in the probiotic-treated group contrasts strongly with observations from a previous smaller study and from our observations regarding the effects of abundant intestinal lactobacilli in patients with short small bowel (SSB) syndrome. We argue here that a lethal combination of mainly proteolytic pancreas enzymes and probiotic therapy resulted in the high mortality rate of the PROPATRIA trial and that elevated levels of lactic acid produced by bacterial fermentation of carbohydrates were a key contributing factor. We suggest that probiotic therapy may not be counter-indicated for the prevention of secondary infections associated with acute pancreatitis, provided that future clinical studies (i) start probiotic therapy immediately after first onset of disease symptoms, (ii) limit the supply of fermentable carbohydrates, (iii) prevent bacterial (over)growth of patient's own intestinal flora and (iv) massively increase the dose of probiotic bacteria.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Ger P A
authors.initials: GP
authors.lastname: Bongaerts
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: René S V M
authors.initials: RS
authors.lastname: Severijnen
mesh_terms: D000208:Acute Disease; D002908:Chronic Disease; D004311:Double-Blind Method; D006801:Humans; D010195:Pancreatitis / Q000628:therapy; D010919:Placebos; D019936:Probiotics
chemical_list: D010919:Placebos