Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose

A Correction to this article was published on 18 February 2019

This article has been updated

Abstract

Background

Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.

Methods

We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.

Results

51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.

Discussion

To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.

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Change history

  • 18 February 2019

    The original version of the article unfortunately contained an error in article title. The corrected title is ‘Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent <Emphasis Type="Italic">Clostridium difficile</Emphasis> Infection: A Comparative Cohort Analysis of High and Low Dose’.

References

  1. 1.

    Lessa FC, Winston LG, McDonald LC. Emerging infections program CdST Burden of clostridium difficile infection in the United States. New Engl J Med. 2015;372:70–2369.

    Article  CAS  Google Scholar 

  2. 2.

    Ma GK, Brensinger CM, Wu Q, Lewis JD. Increasing incidence of multiply recurrent clostridium difficile infection in the United States: a Cohort study. Ann Intern Med. 2017;167:8–152.

    Article  Google Scholar 

  3. 3.

    Sadowsky MJ, Khoruts A. Faecal microbiota transplantation is promising but not a panacea. Nat Microbiol. 2016;1:16015.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Moayyedi P, Yuan Y, Baharith H, Ford AC. Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials. Med J Aust. 2017;207:72–166.

    Article  Google Scholar 

  5. 5.

    Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108:8–500.

    Google Scholar 

  6. 6.

    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 Off Publ Infect Dis Soc Am. 2014;58:22–1515.

    Article  Google Scholar 

  7. 7.

    Staley C, Hamilton MJ, Vaughn BP, et al. Successful resolution of recurrent clostridium difficile infection using freeze-dried, encapsulated fecal microbiota; pragmatic cohort study. Am J Gastroenterol. 2017;112:7–940.

    Article  Google Scholar 

  8. 8.

    Youngster I, Mahabamunuge J, Systrom HK, et al. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med. 2016;14:134. https://doi.org/10.1186/s12916-016-0680-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Hirsch BE, Saraiya N, Poeth K, Schwartz RM, Epstein ME, Honig G. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection. BMC Infect Dis. 2015;15:191. https://doi.org/10.1186/s12879-015-0930-z.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Kao D, Roach B, Silva M, et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent clostridium difficile infection: a randomized clinical trial. Jama. 2017;318:93–1985.

    Article  Google Scholar 

  11. 11.

    Ibekwe VC, Khela MK, Evans DF, Basit AW. A new concept in colonic drug targeting: a combined pH-responsive and bacterially-triggered drug delivery technology. Aliment Pharmacol Ther. 2008;28:6–911.

    Article  Google Scholar 

  12. 12.

    Van Assche G, D’Haens G, Noman M, et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003;125:31–1025.

    Google Scholar 

  13. 13.

    Dodoo CC, Wang J, Basit AW, Stapleton P, Gaisford S. Targeted delivery of probiotics to enhance gastrointestinal stability and intestinal colonisation. Int J Pharm. 2017;530:9–224.

    Article  CAS  Google Scholar 

  14. 14.

    Smith MB, Kassam Z, Burgess J, et al. The International Public Stool Bank: a scalable model for standardized screening and processing of donor stool for fecal microbiota transplantation. Gastroenterology. 2015;148:S-211.

    Article  Google Scholar 

  15. 15.

    Dubois N, Ling K, Osman M, et al. Prospective assessment of donor eligibility for fecal microbiota transplantation at a Public Stool Bank: results from the evaluation of 1387 candidate donors. Open Forum Infect Dis. 2016;2:962.

    Article  Google Scholar 

  16. 16.

    Kozich JJ, Westcott SL, Baxter NT, Highlander SK, Schloss PD. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol. 2013;79:20–5112.

    Article  CAS  Google Scholar 

  17. 17.

    Allegretti JR, Kao D, Sitko J, Fischer M, Kassam Z. Early antibiotic use after fecal microbiota transplantation increases risk of treatment failure. Clin Infect Dis Off Publ Infect Dis Soc Am. 2018;66:5–134.

    Article  Google Scholar 

  18. 18.

    Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66:569–580. https://doi.org/10.1136/gutjnl-2016-313017.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Crobach MJ, Planche T, Eckert C, et al. European society of clinical microbiology and infectious diseases: update of the diagnostic guidance document for clostridium difficile infection. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2016;22:S63–81.

    Google Scholar 

  20. 20.

    Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of clostridium difficile infection in the molecular test Era. JAMA Intern Med. 2015;175:801–1792.

    Article  Google Scholar 

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Authors

Contributions

Author’s contribution

JRA and ZK initiated study concept and design acquisition of data, analysis and interpretation of data, and drafting of the manuscript. YG, ST, and RS analyzed and interpreted microbiome-sequencing results. MF, MB, SS, SB, ES, DLG, ELS, AG participated in data acquisition, interpretation of data and critical revision of the manuscript. HMF, AWB, SRR, MS provided critical revision of manuscript.

Corresponding author

Correspondence to Jessica R. Allegretti.

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Conflict of interest

ZK YG, ST, MS and RS, DG, ELS are employees of Finch Therapeutics. JRA and MF consult for Finch Therapeutics. HMF receives royalties from Phloral. No other conflicts of interest to report for any authors relevant to the work presented in this manuscript.

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Allegretti, J.R., Fischer, M., Sagi, S.V. et al. Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. Dig Dis Sci 64, 1672–1678 (2019). https://doi.org/10.1007/s10620-018-5396-6

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Keywords

  • Fecal microbiota transplantation
  • Microbiome
  • Clostridium difficile infection
  • Fecal capsule