title: Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.
abstract: OBJECTIVE
  Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.
  
  
  OBJECTIVE
  To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection.
  
  
  METHODS
  Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled.
  
  
  METHODS
  Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.
  
  
  METHODS
  The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements.
  
  
  RESULTS
  No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02).
  
  
  CONCLUSIONS
  This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01914731.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston2Harvard Medical School, Boston, Massachusetts3Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Ilan
authors.initials: I
authors.lastname: Youngster
authors.affiliation: Harvard Medical School, Boston, Massachusetts4Department of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: George H
authors.initials: GH
authors.lastname: Russell
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston.
authors.forename: Christina
authors.initials: C
authors.lastname: Pindar
authors.affiliation: Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Ziv-Baran
authors.affiliation: Harvard Medical School, Boston, Massachusetts6Division of Gastroenterology, Massachusetts General Hospital, Boston.
authors.forename: Jenny
authors.initials: J
authors.lastname: Sauk
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston2Harvard Medical School, Boston, Massachusetts.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hohmann
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002214:Capsules; D002648:Child; D016360:Clostridioides difficile; D015925:Cryopreservation; D003967:Diarrhea / Q000209:etiology / Q000628:therapy; D004761:Enterocolitis, Pseudomembranous / Q000150:complications / Q000628:therapy*; D005243:Feces / Q000382:microbiology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D055502:Secondary Prevention; D014180:Transplantation / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002214:Capsules