Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study.
BACKGROUND
Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration.


METHODS
Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires.


RESULTS
A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2-16) relapses prior to study enrollment, with 5 (range, 3-15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5-10) the day prior to FMT to 2 (IQR, 1-2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2-6) before transplant to 8 (IQR, 5-9) after transplant. No serious or unexpected adverse events occurred.


CONCLUSIONS
In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration.


BACKGROUND
NCT01704937.
Division of Infectious Diseases, Massachusetts General Hospital.
Ilan
I
Youngster
Jenny
J
Sauk
Christina
C
Pindar
Robin G
RG
Wilson
Jess L
JL
Kaplan
Mark B
MB
Smith
Eric J
EJ
Alm
Dirk
D
Gevers
George H
GH
Russell
Elizabeth L
EL
Hohmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001691:Biological Therapy / Q000379:methods*; D002648:Child; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000628:therapy*; D003113:Colonoscopy / Q000379:methods; D003967:Diarrhea / Q000382:microbiology / Q000628:therapy*; D005260:Female; D006801:Humans; D007441:Intubation, Gastrointestinal / Q000379:methods; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
Clostridium difficile; fecal microbiota transplant; frozen inoculum; microbiome