Information de reference pour ce titreAccession Number: | 01451458-201406010-00012.
|
Author: | Youngster, Ilan 1,2,3; Sauk, Jenny 2,4; Pindar, Christina 1; Wilson, Robin G. 4; Kaplan, Jess L. 2,5; Smith, Mark B. 6; Alm, Eric J. 6; Gevers, Dirk 7; Russell, George H. 2,5; Hohmann, Elizabeth L. 1,2
|
Institution: | (1)Division of Infectious Diseases, Massachusetts General Hospital (2)Harvard Medical School (3)Division of Infectious Diseases, Boston Children's Hospital (4)Division of Gastroenterology, Massachusetts General Hospital (5)Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston (6)Department of Biological Engineering (7)Broad Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts
|
Title: | |
Source: | Clinical Infectious Diseases. 58(11):1515-1522, June 01, 2014.
|
Abstract: | 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.
Clinical Trials Registration. NCT01704937.
(C) Copyright Oxford University Press 2014.
|
Author Keywords: | fecal microbiota transplant; Clostridium difficile; microbiome; frozen inoculum.
|
References: | 1. Khanna S, Baddour LM, Huskins WC, et al. The epidemiology of Clostridium difficile infection in children: a population-based study Clin Infect Dis. 2013;56:1401-6
2. Jarvis WR, Schlosser J, Jarvis AA, Chinn RY. National point prevalence of Clostridium difficile in US health care facility inpatients, 2008 Am J Infect Control. 2009;37:263-70
3. Kelly CP, LaMont JT. Clostridium difficile-more difficult than ever N Engl J Med. 2008;359:1932-40
4. Sammons JS, Toltzis P, Zaoutis TE. Clostridium difficile infection in children JAMA Pediatr. 2013;167:567-73
5. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection N Engl J Med. 2011;364:422-31
6. Pepin J, Routhier S, Gagnon S, Brazeau I. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada Clin Infect Dis. 2006;42:758-64
7. Pepin J, Valiquette L, Gagnon S, Routhier S, Brazeau I. Outcomes of Clostridium difficile-associated disease treated with metronidazole or vancomycin before and after the emergence of NAP1/027 Am J Gastroenterol. 2007;102:2781-8
8. Vardakas KZ, Polyzos KA, Patouni K, Rafailidis PI, Samonis G, Falagas ME. Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence Int J Antimicrob Agents. 2012;40:1-8
9. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis Nat Rev Microbiol. 2009;7:526-36
10. Petrella LA, Sambol SP, Cheknis A, et al. Decreased cure and increased recurrence rates for Clostridium difficile infection caused by the epidemic C. difficile BI strain Clin Infect Dis. 2012;55:351-7
11. Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea J Infect Dis. 2008;197:435-8
12. Lawley TD, Clare S, Walker AW, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice PLoS Pathog. 2012;8:e1002995
13. Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube Clin Infect Dis. 2003;36:580-5
14. Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation Clin Gastroenterol Hepatol. 2011;9:1044-9
15. Brandt LJ, Aroniadis OC, Mellow M, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection Am J Gastroenterol. 2012;107:1079-87
16. Brandt LJ, Reddy SS. Fecal microbiota transplantation for recurrent clostridium difficile infection J Clin Gastroenterol. 2011;45(suppl):S159-67
17. Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results J Clin Gastroenterol. 2012;46:145-9
18. Mattila E, Uusitalo-Seppala R, Wuorela M, et al. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection Gastroenterology. 2012;142:490-6
19. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile N Engl J Med. 2013;368:407-15
20. Glauser W. Risk and rewards of fecal transplants CMAJ. 2011;183:541-2
21. Guo B, Harstall C, Louie T, Veldhuyzen van Zanten S, Dieleman LA. Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease Aliment Pharmacol Ther. 2012;35:865-75
22. Karadsheh Z, Sule S. Fecal transplantation for the treatment of recurrent Clostridium difficile infection N Am J Med Sci. 2013;5:339-43
23. Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis Am J Gastroenterol. 2013;108:500-8
24. Fridey JL, Townsend MJ, Kessler DA, Gregory KR. A question of clarity: redesigning the American Association Of Blood Banks blood donor history questionnaire-a chronology and model for donor screening Transfus Med Rev. 2007;21:181-204
25. Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection Am J Gastroenterol. 2012;107:761-7
26. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment Semin Radiat Oncol. 2003;13:176-81
27. Caporaso JG, Lauber CL, Walters WA, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms ISME J. 2012;6:1621-4
28. Preheim SP, Perrotta AR, Friedman J, et al. Computational methods for high-throughput comparative analyses of natural microbial communities Methods Enzymol. 2013;531:353-70
29. Sammons JS, Toltzis P, Zaoutis TE. Clostridium difficile infection in children JAMA Pediatr. 2013;167:567-73
30. Village EG. Clostridium difficile infection in infants and children Pediatrics. 2013;131:196-200
31. Kelly CR, Kunde SS, Khoruts A. Guidance on preparing an Investigational New Drug application for fecal microbiota transplantation studies Clin Gastroenterol Hepatol. 2014;12:283-8
|
Language: | English.
|
Document Type: | ARTICLES AND COMMENTARIES.
|
Journal Subset: | Clinical Medicine. Life & Biomedical Sciences.
|
ISSN: | 1058-4838
|
DOI Number: | https://dx.doi.org/10.1093/cid/c...- ouverture dans une nouvelle fenêtre
|
Annotation(s) | |
|
|