title: Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial.
abstract: BACKGROUND
  Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI.
  
  
  METHODS
  In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available.
  
  
  RESULTS
  The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon.
  
  
  CONCLUSIONS
  In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations.
  
  
  BACKGROUND
  NCT01226992.
authors.affiliation: Department of Infection Prevention and Control, University Health Network, Toronto, susy.hota@uhn.ca.|Department of Medicine, University of Toronto.|Department of Medicine, University Health Network.
authors.forename: Susy S
authors.initials: SS
authors.lastname: Hota
authors.affiliation: Department of Medicine, University of Toronto.|Department of Medicine, Markham-Stouffville Hospital, Markham; and.|Department of Medicine, University Health Network.
authors.forename: Valerie
authors.initials: V
authors.lastname: Sales
authors.affiliation: Department of Medicine, University Health Network.|Institute of Health Policy, Management and Evaluation and Dalla Lana School of Public Health, University of Toronto.
authors.forename: George
authors.initials: G
authors.lastname: Tomlinson
authors.affiliation: Department of Infection Prevention and Control, University Health Network, Toronto.|Department of Anaesthesia, University Health Network.
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Salpeter
authors.affiliation: Department of Medicine, University of Toronto.|Department of Microbiology, University Health Network/Sinai Health System.|Department of Laboratory Medicine and Pathobiology, University of Toronto.
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.affiliation: Department of Medicine, University of Toronto.|Department of Medicine, University Health Network.|Toronto General Research Institute, University Health Network, and.
authors.forename: Bryan
authors.initials: B
authors.lastname: Coburn
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, and.|Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Guttman
authors.affiliation: Department of Medicine, University of Toronto.|Department of Microbiology, University Health Network/Sinai Health System.|Department of Laboratory Medicine and Pathobiology, University of Toronto.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.affiliation: Department of Medicine, University of Toronto.|Department of Microbiology, University Health Network/Sinai Health System.|Department of Laboratory Medicine and Pathobiology, University of Toronto.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Poutanen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016360:Clostridioides difficile; D003967:Diarrhea / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy*; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy*; D000069467:Fecal Microbiota Transplantation; D005260:Female; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D009864:Ontario; D012008:Recurrence; D014640:Vancomycin / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: fecal transplantation; intestinal microbiota; randomized controlled trial.; recurrent Clostridium difficile infection; vancomycin taper