Skip to main content
Top
Published in: BMC Infectious Diseases 1/2015

Open Access 01-12-2015 | Research article

Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection

Authors: Bruce E Hirsch, Nimit Saraiya, Kaitlin Poeth, Rebecca M Schwartz, Marcia E Epstein, Gerard Honig

Published in: BMC Infectious Diseases | Issue 1/2015

Login to get access

Abstract

Background

Clostridium difficile infection (CDI), a complication of antibiotic-induced injury to the gut microbiome, is a prevalent and dangerous cause of infectious diarrhea. Antimicrobial therapy for CDI is typically effective for acute symptoms, but up to one third of patients later experience recurrent CDI. Fecal-derived microbiota transplantation (FMT) can ameliorate the underlying dysbiosis and is highly effective for recurrent CDI. Traditional methods of FMT are limited by patient discomfort, risk and inefficient procedures. Many individuals with recurrent CDI have extensive comorbidities and advanced age. Widespread use of FMT requires strategies that are non-invasive, scalable and applicable across healthcare settings.

Methods

A method to facilitate microbiota transfer was developed. Fecal samples were collected and screened for potential pathogens. Bacteria were purified, concentrated, cryopreserved and formulated into multi-layered capsules. Capsules were administered to patients with recurrent CDI, who were then monitored for 90 days.

Results

Thirteen women and six men with recurrent CDI were provided with microbiota transfer with orally administered capsules. The procedure was well tolerated. Thirteen individuals responded to a single course. Four patients were cured after a second course. There were 2 failures. The cumulative clinical cure rate of 89% is similar to the rates achieved with reported fecal-derived transplantation procedures.

Conclusions

Recurrent CDI represents a profound dysbiosis and a debilitating chronic disease. Stable cure can be achieved by restoring the gut microbiome with an effective, well-tolerated oral capsule treatment. This strategy of microbiota transfer can be widely applied and is particularly appropriate for frail patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care–associated infections. N Engl J Med. 2014;370(13):1198–208.PubMedCrossRef Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care–associated infections. N Engl J Med. 2014;370(13):1198–208.PubMedCrossRef
3.
go back to reference Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009: statistical brief #124. 2012. Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009: statistical brief #124. 2012.
4.
go back to reference Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the united states. N Engl J Med. 2015;372(9):825–34.PubMedCrossRef Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the united states. N Engl J Med. 2015;372(9):825–34.PubMedCrossRef
5.
go back to reference Lipp MJ, Nero DC, Callahan MA. Impact of hospital-acquired Clostridium difficile. J Gastroenterol Hepatol. 2012;27(11):1733–7.PubMedCrossRef Lipp MJ, Nero DC, Callahan MA. Impact of hospital-acquired Clostridium difficile. J Gastroenterol Hepatol. 2012;27(11):1733–7.PubMedCrossRef
6.
go back to reference Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea Due to Clostridium difficile. Clin Infect Dis. 2002;34(3):346–53.PubMedCrossRef Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea Due to Clostridium difficile. Clin Infect Dis. 2002;34(3):346–53.PubMedCrossRef
7.
go back to reference Elixhauser A, Steiner C, Gould C. Readmissions following Hospitalizations with Clostridium difficile Infections, 2009: Statistical Brief #145. Rockville MD: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs; 2006. Elixhauser A, Steiner C, Gould C. Readmissions following Hospitalizations with Clostridium difficile Infections, 2009: Statistical Brief #145. Rockville MD: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs; 2006.
9.
go back to reference Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18:21–7.PubMedCrossRef Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18:21–7.PubMedCrossRef
10.
go back to reference Khanna S, Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings. Expert Rev Gastroenterol Hepatol. 2010;4(4):409–16.PubMedCrossRef Khanna S, Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings. Expert Rev Gastroenterol Hepatol. 2010;4(4):409–16.PubMedCrossRef
11.
go back to reference Bakken JS. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anal Chem. 2009;15(6):285–9. Bakken JS. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anal Chem. 2009;15(6):285–9.
12.
go back to reference Pépin J, Alary M-E, Valiquette L, Raiche E, Ruel J, Fulop K, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40(11):1591–7.PubMedCrossRef Pépin J, Alary M-E, Valiquette L, Raiche E, Ruel J, Fulop K, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40(11):1591–7.PubMedCrossRef
13.
go back to reference Figueroa I, Johnson S, Sambol SP, Goldstein EJC, Citron DM, Gerding DN. Relapse versus reinfection: recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin. Clin Infect Dis. 2012;55 suppl 2:S104–9.PubMedCentralPubMedCrossRef Figueroa I, Johnson S, Sambol SP, Goldstein EJC, Citron DM, Gerding DN. Relapse versus reinfection: recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin. Clin Infect Dis. 2012;55 suppl 2:S104–9.PubMedCentralPubMedCrossRef
14.
go back to reference Surawicz CM. Treatment of recurrent Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol. 2004;1(1):32–8.PubMedCrossRef Surawicz CM. Treatment of recurrent Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol. 2004;1(1):32–8.PubMedCrossRef
15.
go back to reference Petrella LA, Sambol SP, Cheknis A, Nagaro K, Kean Y, Sears PS, 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(3):351–7.PubMedCentralPubMedCrossRef Petrella LA, Sambol SP, Cheknis A, Nagaro K, Kean Y, Sears PS, 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(3):351–7.PubMedCentralPubMedCrossRef
16.
go back to reference Blaser M, Bork P, Fraser C, Knight R, Wang J. The microbiome explored: recent insights and future challenges. Nat Rev Microbiol. 2013;11(3):213–7.PubMedCrossRef Blaser M, Bork P, Fraser C, Knight R, Wang J. The microbiome explored: recent insights and future challenges. Nat Rev Microbiol. 2013;11(3):213–7.PubMedCrossRef
18.
go back to reference Tosh PK, McDonald LC. Infection control in the multidrug-resistant era: tending the human microbiome. Clin Infect Dis. 2011;54(5):707–13.PubMedCrossRef Tosh PK, McDonald LC. Infection control in the multidrug-resistant era: tending the human microbiome. Clin Infect Dis. 2011;54(5):707–13.PubMedCrossRef
19.
go back to reference Abt MC, Pamer EG. Commensal bacteria mediated defenses against pathogens. Curr Opin Immunol. 2014;29:16–22.PubMedCrossRef Abt MC, Pamer EG. Commensal bacteria mediated defenses against pathogens. Curr Opin Immunol. 2014;29:16–22.PubMedCrossRef
20.
go back to reference Louie TJ, Cannon K, Byrne B, Emery J, Ward L, Eyben M, et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;55 suppl 2:S132–42.PubMedCentralPubMedCrossRef Louie TJ, Cannon K, Byrne B, Emery J, Ward L, Eyben M, et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;55 suppl 2:S132–42.PubMedCentralPubMedCrossRef
21.
go back to reference Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-Old fecal microbiota transplantation? Am J Gastroenterol. 2012;107(11):1755–5.PubMedCrossRef Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-Old fecal microbiota transplantation? Am J Gastroenterol. 2012;107(11):1755–5.PubMedCrossRef
22.
go back to reference Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854–9.PubMed Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854–9.PubMed
23.
go back to reference van der Waaij D, Vossen JM, Altes CK, Hartgrink C. Reconventionalization following antibiotic decontamination in man and animals. Am J Clin Nutr. 1977;30(11):1887–95.PubMed van der Waaij D, Vossen JM, Altes CK, Hartgrink C. Reconventionalization following antibiotic decontamination in man and animals. Am J Clin Nutr. 1977;30(11):1887–95.PubMed
24.
go back to reference Heidt PJ, van der Waaij D, Vossen JM, Hendriks WD. The use of a human donor flora for recontamination following antibiotic decontamination. Prog Food Nutr Sci. 1983;7(3–4):53–63.PubMed Heidt PJ, van der Waaij D, Vossen JM, Hendriks WD. The use of a human donor flora for recontamination following antibiotic decontamination. Prog Food Nutr Sci. 1983;7(3–4):53–63.PubMed
25.
go back to reference Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, 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):1515–22.PubMedCentralPubMedCrossRef Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, 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):1515–22.PubMedCentralPubMedCrossRef
26.
go back to reference Vaishnavi C. Fecal microbiota transplantation for management of Clostridium difficile infection. Indian J Gastroenterol. 2014;33(4):301–7.PubMedCrossRef Vaishnavi C. Fecal microbiota transplantation for management of Clostridium difficile infection. Indian J Gastroenterol. 2014;33(4):301–7.PubMedCrossRef
27.
go back to reference Austin M, Mellow M, Tierney WM. Fecal microbiota transplantation in the treatment of Clostridium difficile infections. Am J Med. 2014;127(6):479–83.PubMedCrossRef Austin M, Mellow M, Tierney WM. Fecal microbiota transplantation in the treatment of Clostridium difficile infections. Am J Med. 2014;127(6):479–83.PubMedCrossRef
28.
go back to reference Brandt LJ, Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointestinal endoscopy. 2013;78(2):240–9.PubMedCrossRef Brandt LJ, Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointestinal endoscopy. 2013;78(2):240–9.PubMedCrossRef
29.
go back to reference Bakken JS, Polgreen PM, Beekmann SE, Riedo FX, Streit JA. Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians. Anal Chem. 2013;24:20–4. Bakken JS, Polgreen PM, Beekmann SE, Riedo FX, Streit JA. Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians. Anal Chem. 2013;24:20–4.
30.
go back to reference Borody TJ, Brandt LJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: a new standard treatment option for Clostridium difficile infection. Expert Rev Anti Infect Ther. 2013;11(5):447–9.PubMedCrossRef Borody TJ, Brandt LJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: a new standard treatment option for Clostridium difficile infection. Expert Rev Anti Infect Ther. 2013;11(5):447–9.PubMedCrossRef
31.
go back to reference Brandt LJ, Aroniadis OC, Mellow M, Kanatzar A, Kelly C, Park T, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(7):1079–87.PubMedCrossRef Brandt LJ, Aroniadis OC, Mellow M, Kanatzar A, Kelly C, Park T, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(7):1079–87.PubMedCrossRef
32.
go back to reference Burke KE, Lamont JT. Fecal transplantation for recurrent Clostridium difficile infection in older adults: a review. J Am Geriatr Soc. 2013;61(8):1394–8.PubMedCrossRef Burke KE, Lamont JT. Fecal transplantation for recurrent Clostridium difficile infection in older adults: a review. J Am Geriatr Soc. 2013;61(8):1394–8.PubMedCrossRef
33.
go back to reference de Vos WM. Fame and future of faecal transplantations – developing next-generation therapies with synthetic microbiomes. Microbial Biotechnology. 2013;6(4):316–25.PubMedCentralPubMedCrossRef de Vos WM. Fame and future of faecal transplantations – developing next-generation therapies with synthetic microbiomes. Microbial Biotechnology. 2013;6(4):316–25.PubMedCentralPubMedCrossRef
34.
35.
go back to reference Fuentes S, van Nood E, Tims S, Heikamp-de Jong I, ter Braak CJF, Keller JJ, et al. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection. ISME J. 2014;8:1621–33.PubMedCrossRef Fuentes S, van Nood E, Tims S, Heikamp-de Jong I, ter Braak CJF, Keller JJ, et al. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection. ISME J. 2014;8:1621–33.PubMedCrossRef
36.
go back to reference Gens KD, Elshaboury RH, Holt JS. Fecal microbiota transplantation and emerging treatments for Clostridium difficile infection. J Pharm Pract. 2013;26(5):498–505.PubMedCrossRef Gens KD, Elshaboury RH, Holt JS. Fecal microbiota transplantation and emerging treatments for Clostridium difficile infection. J Pharm Pract. 2013;26(5):498–505.PubMedCrossRef
37.
go back to reference Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994–1002.PubMedCrossRef Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994–1002.PubMedCrossRef
38.
go back to reference Högenauer C, Kump PK, Krause R. Tempered enthusiasm for fecal transplantation. Clin Infect Dis. 2014;59(9):1348–9.PubMedCrossRef Högenauer C, Kump PK, Krause R. Tempered enthusiasm for fecal transplantation. Clin Infect Dis. 2014;59(9):1348–9.PubMedCrossRef
39.
go back to reference Jorup-Ronstrom C, Hakanson A, Sandell S, Edvinsson O, Midtvedt T, Persson AK, et al. Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol. 2012;47(5):548–52.PubMedCrossRef Jorup-Ronstrom C, Hakanson A, Sandell S, Edvinsson O, Midtvedt T, Persson AK, et al. Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol. 2012;47(5):548–52.PubMedCrossRef
40.
go back to reference Kelly CP. Fecal microbiota transplantation — an old therapy comes of age. N Engl J Med. 2013;368(5):474–5.PubMedCrossRef Kelly CP. Fecal microbiota transplantation — an old therapy comes of age. N Engl J Med. 2013;368(5):474–5.PubMedCrossRef
41.
go back to reference Khoruts A, Sadowsky MJ. Therapeutic transplantation of the distal gut microbiota. Mucosal Immunol. 2011;4(1):4–7.PubMedCrossRef Khoruts A, Sadowsky MJ. Therapeutic transplantation of the distal gut microbiota. Mucosal Immunol. 2011;4(1):4–7.PubMedCrossRef
42.
go back to reference Moore T, Rodriguez A, Bakken JS. Fecal microbiota transplantation: a practical update for the infectious disease specialist. Clin Infect Dis. 2014;58(4):541–5.PubMedCrossRef Moore T, Rodriguez A, Bakken JS. Fecal microbiota transplantation: a practical update for the infectious disease specialist. Clin Infect Dis. 2014;58(4):541–5.PubMedCrossRef
43.
go back to reference Pamer EG. Fecal microbiota transplantation: effectiveness, complexities, and lingering concerns. Mucosal Immunol. 2014;7(2):210–4.PubMedCrossRef Pamer EG. Fecal microbiota transplantation: effectiveness, complexities, and lingering concerns. Mucosal Immunol. 2014;7(2):210–4.PubMedCrossRef
44.
45.
go back to reference Ritter AS, Petri WAJ. New developments in chemotherapeutic options for Clostridium difficile colitis. Curr Opin Infect Dis. 2013;26(5):461–70.PubMed Ritter AS, Petri WAJ. New developments in chemotherapeutic options for Clostridium difficile colitis. Curr Opin Infect Dis. 2013;26(5):461–70.PubMed
46.
go back to reference Rubin TA, Gessert CE, Aas J, Bakken JS. Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series. Anal Chem. 2013;19:22–6. Rubin TA, Gessert CE, Aas J, Bakken JS. Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series. Anal Chem. 2013;19:22–6.
47.
go back to reference Russell GH, Kaplan JL, Youngster I, Baril-Dore M, Schindelar L, Hohmann E, et al. Fecal transplant for recurrent Clostridium difficile infection in children with and without inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2014;58(5):588–92.PubMedCrossRef Russell GH, Kaplan JL, Youngster I, Baril-Dore M, Schindelar L, Hohmann E, et al. Fecal transplant for recurrent Clostridium difficile infection in children with and without inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2014;58(5):588–92.PubMedCrossRef
48.
go back to reference Senior K. Faecal transplantation for recurrent C difficile diarrhoea. Lancet Infect Dis. 2013;13(3):200–1.PubMedCrossRef Senior K. Faecal transplantation for recurrent C difficile diarrhoea. Lancet Infect Dis. 2013;13(3):200–1.PubMedCrossRef
49.
go back to reference Tarr P. Fecal transplants for Clostridium difficile: Microbial Messiah or medical misadventure. In: Public Workshop: Fecal Microbiota for Transplantation: May 2013 2013; National Institutes of Health: Food & Drug Administration. 2013. Tarr P. Fecal transplants for Clostridium difficile: Microbial Messiah or medical misadventure. In: Public Workshop: Fecal Microbiota for Transplantation: May 2013 2013; National Institutes of Health: Food & Drug Administration. 2013.
50.
go back to reference Taur Y, Pamer EG. Harnessing microbiota to kill a pathogen: fixing the microbiota to treat Clostridium difficile infections. Nat Med. 2014;20(3):246–7.PubMedCrossRef Taur Y, Pamer EG. Harnessing microbiota to kill a pathogen: fixing the microbiota to treat Clostridium difficile infections. Nat Med. 2014;20(3):246–7.PubMedCrossRef
51.
go back to reference van Nood E, Speelman P, Nieuwdorp M, Keller J. Fecal microbiota transplantation: facts and controversies. Curr Opin Gastroenterol. 2014;30(1):34–9.PubMedCrossRef van Nood E, Speelman P, Nieuwdorp M, Keller J. Fecal microbiota transplantation: facts and controversies. Curr Opin Gastroenterol. 2014;30(1):34–9.PubMedCrossRef
52.
go back to reference van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15.PubMedCrossRef van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15.PubMedCrossRef
54.
go back to reference Ben-Amor K, Heilig H, Smidt H, Vaughan EE, Abee T, de Vos WM. Genetic diversity of viable, injured, and dead fecal bacteria assessed by fluorescence-activated cell sorting and 16S rRNA gene analysis. Appl Environ Microbiol. 2005;71(8):4679–89.PubMedCentralPubMedCrossRef Ben-Amor K, Heilig H, Smidt H, Vaughan EE, Abee T, de Vos WM. Genetic diversity of viable, injured, and dead fecal bacteria assessed by fluorescence-activated cell sorting and 16S rRNA gene analysis. Appl Environ Microbiol. 2005;71(8):4679–89.PubMedCentralPubMedCrossRef
56.
go back to reference Juang P, Hardesty JS. Role of fidaxomicin for the treatment of Clostridium difficile infection. J Pharm Pract. 2013;26(5):491–7.PubMedCrossRef Juang P, Hardesty JS. Role of fidaxomicin for the treatment of Clostridium difficile infection. J Pharm Pract. 2013;26(5):491–7.PubMedCrossRef
57.
go back to reference Konijeti GG, Sauk J, Shrime MG, Gupta M, Ananthakrishnan AN. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis. Clin Infect Dis. 2014;58(11):1507–14.PubMedCentralPubMedCrossRef Konijeti GG, Sauk J, Shrime MG, Gupta M, Ananthakrishnan AN. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis. Clin Infect Dis. 2014;58(11):1507–14.PubMedCentralPubMedCrossRef
59.
go back to reference Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010;362(3):197–205.PubMedCrossRef Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010;362(3):197–205.PubMedCrossRef
60.
go back to reference Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–30.PubMedCentralPubMedCrossRef Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–30.PubMedCentralPubMedCrossRef
61.
go back to reference Liévin-Le Moal V, Servin AL. The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota. Clin Microbiol Rev. 2006;19(2):315–37.PubMedCentralPubMedCrossRef Liévin-Le Moal V, Servin AL. The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota. Clin Microbiol Rev. 2006;19(2):315–37.PubMedCentralPubMedCrossRef
62.
go back to reference Clemente Jose C, Ursell Luke K, Parfrey Laura W, Knight R. The impact of the Gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258–70.PubMedCrossRef Clemente Jose C, Ursell Luke K, Parfrey Laura W, Knight R. The impact of the Gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258–70.PubMedCrossRef
63.
go back to reference Vincent C, Stephens D, Loo V, Edens T, Behr M, Dewar K, et al. Reductions in intestinal clostridiales precede the development of nosocomial Clostridium difficile infection. Microbiology. 2013;1(1):18. Vincent C, Stephens D, Loo V, Edens T, Behr M, Dewar K, et al. Reductions in intestinal clostridiales precede the development of nosocomial Clostridium difficile infection. Microbiology. 2013;1(1):18.
65.
go back to reference Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66.PubMedCrossRef Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66.PubMedCrossRef
66.
go back to reference Agito MD, Atreja A, Rizk MK. Fecal microbiota transplantation for recurrent C difficile infection: ready for prime time? Cleve Clin J Med. 2013;80(2):101–8.PubMedCrossRef Agito MD, Atreja A, Rizk MK. Fecal microbiota transplantation for recurrent C difficile infection: ready for prime time? Cleve Clin J Med. 2013;80(2):101–8.PubMedCrossRef
67.
go back to reference Weingarden AR, Chen C, Bobr A, Yao D, Lu Y, Nelson VM, et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am J Physiol Gastrointest Liver Physiol. 2013;306(4):G310–9.PubMedCentralPubMedCrossRef Weingarden AR, Chen C, Bobr A, Yao D, Lu Y, Nelson VM, et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am J Physiol Gastrointest Liver Physiol. 2013;306(4):G310–9.PubMedCentralPubMedCrossRef
68.
go back to reference You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med. 2008;148(8):632–3.PubMedCrossRef You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med. 2008;148(8):632–3.PubMedCrossRef
69.
go back to reference 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(5):580–5.PubMedCrossRef 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(5):580–5.PubMedCrossRef
70.
go back to reference Patel NC, Griesbach CL, DiBaise JK, Orenstein R. Fecal microbiota transplant for recurrent Clostridium difficile infection: mayo clinic in Arizona experience. Mayo Clin Proc. 2013;88(8):799–805.PubMedCrossRef Patel NC, Griesbach CL, DiBaise JK, Orenstein R. Fecal microbiota transplant for recurrent Clostridium difficile infection: mayo clinic in Arizona experience. Mayo Clin Proc. 2013;88(8):799–805.PubMedCrossRef
71.
go back to reference Rohlke F, Surawicz CM, Stollman N. Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. J Clin Gastroenterol. 2010;44(8):567–70. 510.1097/MCG.1090b1013e3181dadb1010.PubMedCrossRef Rohlke F, Surawicz CM, Stollman N. Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. J Clin Gastroenterol. 2010;44(8):567–70. 510.1097/MCG.1090b1013e3181dadb1010.PubMedCrossRef
72.
go back to reference Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol. 2000;95(11):3283–5.PubMed Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol. 2000;95(11):3283–5.PubMed
73.
go back to reference Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8(10), e1002995.PubMedCentralPubMedCrossRef Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8(10), e1002995.PubMedCentralPubMedCrossRef
74.
go back to reference Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2014;517:205–8.PubMedCentralPubMedCrossRef Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2014;517:205–8.PubMedCentralPubMedCrossRef
75.
go back to reference 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(5):761–7.PubMedCrossRef 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(5):761–7.PubMedCrossRef
76.
go back to reference Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. ORal, capsulized, frozen fecal microbiota transplantation for relapsing clostridium difficile infection. JAMA. 2014;312(17):1772–8.PubMedCrossRef Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. ORal, capsulized, frozen fecal microbiota transplantation for relapsing clostridium difficile infection. JAMA. 2014;312(17):1772–8.PubMedCrossRef
77.
go back to reference Bakken JS. Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent clostridium difficile infection. Clin Infect Dis. 2014;59(6):858–61.PubMedCrossRef Bakken JS. Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent clostridium difficile infection. Clin Infect Dis. 2014;59(6):858–61.PubMedCrossRef
78.
go back to reference Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249–57.PubMedCrossRef Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249–57.PubMedCrossRef
79.
go back to reference Kim K-H, Fekety R, Batts DH, Brown D, Cudmore M, Silva J, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis. 1981;143(1):42–50.PubMedCrossRef Kim K-H, Fekety R, Batts DH, Brown D, Cudmore M, Silva J, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis. 1981;143(1):42–50.PubMedCrossRef
80.
go back to reference Lawley TD, Clare S, Walker AW, Goulding D, Stabler RA, Croucher N, et al. Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect Immun. 2009;77(9):3661–9.PubMedCentralPubMedCrossRef Lawley TD, Clare S, Walker AW, Goulding D, Stabler RA, Croucher N, et al. Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect Immun. 2009;77(9):3661–9.PubMedCentralPubMedCrossRef
81.
go back to reference Cohen Stuart HMD, Gerding Dale NMD, Stuart Johnson MD, Kelly Ciaran PMD, Loo Vivian GMD, McDonald LCMD, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Cont Hosp Ep. 2010;31(5):431–55.CrossRef Cohen Stuart HMD, Gerding Dale NMD, Stuart Johnson MD, Kelly Ciaran PMD, Loo Vivian GMD, McDonald LCMD, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Cont Hosp Ep. 2010;31(5):431–55.CrossRef
Metadata
Title
Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection
Authors
Bruce E Hirsch
Nimit Saraiya
Kaitlin Poeth
Rebecca M Schwartz
Marcia E Epstein
Gerard Honig
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2015
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-015-0930-z

Other articles of this Issue 1/2015

BMC Infectious Diseases 1/2015 Go to the issue