Fecal Microbiota Transplantation for the Management of Clostridium difficile Infection

Infectious Disease Clinics of North America

Volumn 29, Issue 1, 2015, Pages 109-122

  Rao, Krishna ^a,b   Young, Vincent B ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b VA ANN ARBOR HEALTHCARE SYSTEM   (United States)

Author keywords

Clostridium difficile; Colitis; Fecal microbiota transplantation; Microbiome; Nonantibiotic treatment; Recurrent C difficile infection

Indexed keywords

ANTIBIOTIC AGENT; FIDAXOMICIN; METRONIDAZOLE; RIFAXIMIN; VANCOMYCIN;

ABDOMINAL CRAMP; ANTIBIOTIC THERAPY; BACTERIAL COLONIZATION; BIOLOGICAL THERAPY; BLOATING; CLOSTRIDIUM DIFFICILE INFECTION; COLONOSCOPY; CONSTIPATION; DIARRHEA; DONOR SELECTION; FECAL MICROBIOTA TRANSPLANTATION; FECES MICROFLORA; HUMAN; IMMUNOCOMPROMISED PATIENT; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; INTESTINE LAVAGE; IRRITABLE COLON; LOW DRUG DOSE; NASOGASTRIC TUBE; NONHUMAN; PATHOGENESIS; PEPTOCLOSTRIDIUM DIFFICILE; RECURRENT INFECTION; RETREATMENT; REVIEW; CLOSTRIDIUM INFECTIONS; DISEASE MANAGEMENT; FECES; GASTROINTESTINAL TRACT; INTESTINAL DISEASES; MICROBIOLOGY; MICROFLORA; PROCEDURES;

BIOLOGICAL THERAPY; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM INFECTIONS; DISEASE MANAGEMENT; FECES; GASTROINTESTINAL TRACT; HUMANS; INTESTINAL DISEASES; MICROBIOTA;

EID: 84922764903     PISSN: 08915520     EISSN: 15579824     Source Type: Journal    
DOI: 10.1016/j.idc.2014.11.009     Document Type: Review

References (70)

1. Yatsunenko T., Rey F.E., Manary M.J., et al. Human gut microbiome viewed across age and geography. Nature 2012, 486(7402):222-227.
2. Van der Waaij D., Berghuis-de Vries J.M., Lekkerkerk-van der Wees J.E. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. Epidemiol Infect 1971, 69(03):405-411.
3. Vollaard E., Clasener H. Colonization resistance. Antimicrob Agents Chemother 1994, 38(3):409.
4. Britton R.A., Young V.B. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology 2014, 146(6):1547-1553.
5. Theriot C.M., Koenigsknecht M.J., Carlson P.E., et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun 2014, 5:3114.
6. Samore M.H., DeGirolami P.C., Tlucko A., et al. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994, 18(2):181-187.
7. Riggs M.M., Sethi A.K., Zabarsky T.F., et al. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin Infect Dis 2007, 45(8):992-998.
8. Bartlett J.G. Treatment of antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1984, 6(Suppl 1):S235-S241.
9. Olson M.M., Shanholtzer C.J., Lee J.T., et al. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994, 15(6):371-381.
10. Debast S.B., Bauer M.P., Kuijper E.J. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 2014, 20(Suppl 2):1-26.
11. McDonald L.C., Coignard B., Dubberke E., et al. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007, 28(2):140-145.
12. Figueroa I., Johnson S., Sambol S.P., et al. Relapse versus reinfection: recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin. Clin Infect Dis 2012, 55(Suppl 2):S104-S109.
13. Eyre D.W., Babakhani F., Griffiths D., et al. Whole-genome sequencing demonstrates that fidaxomicin is superior to vancomycin for preventing reinfection and relapse of infection with Clostridium difficile. JInfect Dis 2014, 209(9):1446-1451.
14. Bakken J.S. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anaerobe 2009, 15(6):285-289.
15. Huebner E.S., Surawicz C.M. Treatment of recurrent Clostridium difficile diarrhea. Gastroenterol Hepatol 2006, 2(3):203-208.
16. Borody T.J., Warren E.F., Leis S.M., et al. Bacteriotherapy using fecal flora: toying with human motions. JClin Gastroenterol 2004, 38(6):475-483.
17. McFarland L.V., Elmer G.W., Surawicz C.M. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol 2002, 97(7):1769-1775.
18. Garey K.W., Ghantoji S.S., Shah D.N., et al. Arandomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection. JAntimicrob Chemother 2011, 66(12):2850-2855.
19. Johnson S., Gerding D.N. Fidaxomicin 'chaser' regimen following vancomycin for patients with multiple C. difficile recurrences. Clin Infect Dis 2012, 56(2):309-310.
20. Kyne L., Warny M., Qamar A., et al. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 2001, 357(9251):189-193.
21. Crook D.W., Walker A.S., Kean Y., et al. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis 2012, 55(Suppl 2):S93-S103.
22. Abou Chakra C.N., Pepin J., Sirard S., et al. Risk factors for recurrence, complications and mortality in Clostridium difficile infection: a systematic review. PLoS One 2014, 9(6):e98400.
23. Chang J.Y., Antonopoulos D.A., Kalra A., et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. JInfect Dis 2008, 197(3):435-438.
24. O'Horo J., Safdar N. The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review. Int J Infect Dis 2009, 13(6):663-667.
25. Cornely O.A., Miller M.A., Louie T.J., et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis 2012, 55(Suppl 2):S154-S161.
26. Bakken J.S., Polgreen P.M., Beekmann S.E., et al. Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians. Anaerobe 2013, 24:20-24.
27. Britton R.A., Young V.B. Interaction between the intestinal microbiota and host in Clostridium difficile colonization resistance. Trends Microbiol 2012, 20(7):313-319.
28. Seekatz A.M., Aas J., Gessert C.E., et al. Recovery of the gut microbiome following fecal microbiota transplantation. MBio 2014, 5(3):e00893-e00914.
29. Weingarden A.R., Chen C., Bobr A., et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am J Physiol Gastrointest Liver Physiol 2014, 306(4):G310-G319.
30. Schwan A., Sjolin S., Trottestam U., et al. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. Lancet 1983, 322(8354):845.
31. Zhang F., Luo W., Shi Y., et al. Should we standardize the 1,700-year-old fecal microbiota transplantation?. Am J Gastroenterol 2012, 107(11):1755.
32. Eiseman B., Silen W., Bascom G.S., et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958, 44(5):854-859.
33. Aas J., Gessert C.E., Bakken J.S. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis 2003, 36(5):580-585.
34. Persky S.E., Brandt L.J. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol 2000, 95(11):3283-3285.
35. Silverman M.S., Davis I., Pillai D.R. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol 2010, 8(5):471-473.
36. Bakken J.S., Borody T., Brandt L.J., et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol 2011, 9(12):1044-1049.
37. Gough E., Shaikh H., Manges A.R. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 2011, 53(10):994-1002.
38. Kassam Z., Lee C.H., Yuan Y., et al. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013, 108(4):500-508.
39. Hamilton M.J., Weingarden A.R., Sadowsky M.J., et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 2012, 107(5):761-767.
40. Youngster I., Russell G.H., Pindar C., et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 2014, 312(17):1772-1778. 10.1001/jama.2014.13875.
41. Rebiotix Inc Microbiota restoration therapy for recurrent Clostridium difficile-associated diarrhea (PUNCH CD) 2000, ClinicalTrials.gov. [Internet], National Library of Medicine (US), Bethesda (MD), Available at:, Accessed July 1, 2014. NLM Identifier: NCT01925417. http://clinicaltrials.gov/ct2/show/NCT01925417.
42. Draft guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. U.S. Department of Health and Human Services, Food and Drug Administration. Available at: . Accessed July 1, 2014. http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vaccines/ucm387023.htm.
43. Sha S., Liang J., Chen M., et al. Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children. Aliment Pharmacol Ther 2014, 39(10):1003-1032.
44. Kassam Z., Hundal R., Marshall J.K., et al. Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection. Arch Intern Med 2012, 172(2):191-193.
45. Kelly C.R., Ihunnah C., Fischer M., et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol 2014, 109(7):1065-1071.
46. Dutta S.K., Girotra M., Garg S., et al. Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol 2014, 12(9):1572-1576.
47. Friedman-Moraco R.J., Mehta A.K., Lyon G.M., et al. Fecal microbiota transplantation for refractory Clostridium difficile colitis in solid organ transplant recipients. Am J Transplant 2014, 14(2):477-480.
48. Emanuelsson F., Claesson B.E., Ljungström L., et al. Faecal microbiota transplantation and bacteriotherapy for recurrent Clostridium difficile infection: a retrospective evaluation of 31 patients. Scand J Infect Dis 2014, 46(2):89-97.
49. van Nood E., Vrieze A., Nieuwdorp M., et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med 2013, 368(5):407-415.
50. Youngster I., Sauk J., Pindar C., et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis 2014, 58(11):1515-1522.
51. University Health Network Toronto Oral vancomycin followed by fecal transplant versus tapering oral vancomycin 2000, ClinicalTrials.gov. [Internet], National Library of Medicine (US), Bethesda (MD), Available at:, Accessed July 1, 2014. NLM Identifier: NCT01226992. http://clinicaltrials.gov/ct2/show/NCT01226992.
52. Tel-Aviv Sourasky Medical Center Transplantation of fecal microbiota for Clostridium difficile infection 2000, ClinicalTrials.gov. [Internet], National Library of Medicine (US), Bethesda (MD), Available at:, Accessed July 1, 2014. NLM Identifier: NCT01958463. http://clinicaltrials.gov/ct2/show/NCT01958463.
53. Hadassah Medical Organization Efficacy and safety of fecal microbiota transplantation for severe Clostridium difficile associated colitis 2000, ClinicalTrials.gov. [Internet], National Library of Medicine (US), Bethesda (MD), Available at:, Accessed July 1, 2014. NLM Identifier: NCT01959048. http://clinicaltrials.gov/ct2/show/NCT01959048.
54. University Hospital Tuebingen Fecal microbiota transplantation in recurrent or refractory Clostridium difficile colitis (TOCSIN) 2000, ClinicalTrials.gov. [Internet], National Library of Medicine (US), Bethesda (MD), Available at:, Accessed July 1, 2014. NLM Identifier: NCT01942447. http://clinicaltrials.gov/ct2/show/NCT01942447.
55. Duke University Stool transplants to treat refractory Clostridium difficile colitis 2000, ClinicalTrials.gov. [Internet], National Library of Medicine (US), Bethesda (MD), Available at:, Accessed July 1, 2014. NLM Identifier: NCT02127398. http://clinicaltrials.gov/ct2/show/NCT02127398.
56. Lofgren E.T., Moehring R.W., Anderson D.J., et al. Amathematical model to evaluate the routine use of fecal microbiota transplantation to prevent incident and recurrent Clostridium difficile infection. Infect Control Hosp Epidemiol 2013, 35(1):18-27.
57. Rao K., Young V.B., Aronoff D.M. Commentary: fecal microbiota therapy: ready for prime time?. Infect Control Hosp Epidemiol 2014, 35(1):28-30.
58. Neemann K., Eichele D.D., Smith P.W., et al. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient. Transpl Infect Dis 2012, 14(6):E161-E165.
59. Trubiano J.A., Gardiner B., Kwong J.C., et al. Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit. Eur J Gastroenterol Hepatol 2013, 25(2):255-257.
60. Gallegos-Orozco J., Paskvan-Gawryletz C., Gurudu S., et al. Successful colonoscopic fecal transplant for severe acute Clostridium difficile pseudomembranous colitis. Rev Gastroenterol Mex 2011, 77(1):40-42.
61. You D.M., Franzos M.A., Holman R.P. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med 2008, 148(8):632-633.
62. Solari P.R., Fairchild P.G., Noa L.J., et al. Tempered enthusiasm for fecal transplant. Clin Infect Dis 2014, 59(2):319.
63. De Leon L.M., Watson J.B., Kelly C.R. Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol 2013, 11(8):1036-1038.
64. Angelberger S., Reinisch W., Makristathis A., et al. Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 2013, 108(10):1620-1630.
65. Kump P.K., Gröchenig H.P., Lackner S., et al. Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis 2013, 19(10):2155-2165.
66. Besselink M.G., van Santvoort H.C., Buskens E., et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 2008, 371(9613):651-659.
67. Sekirov I., Russell S.L., Antunes L.C., et al. Gut microbiota in health and disease. Physiol Rev 2010, 90(3):859-904.
68. Brandt L.J., Aroniadis O.C., Mellow M., et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 2012, 107(7):1079-1087.
69. Guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. U.S. Department of Health and Human Services, Food and Drug Administration. Available at: . Accessed July 1, 2014. http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vaccines/ucm361379.htm.
70. Zipursky J.S., Sidorsky T.I., Freedman C.A., et al. Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Clin Infect Dis 2012, 55(12):1652-1658.