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Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure

Abstract

Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered “much better” in 17 patients (73.9%); “somewhat better” in 3 patients (13.0%); and “about the same” in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn’s disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48–96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported “much better” overall health following FMT.

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References

  1. Dubberke ER, Olsen MA (2012) Burden of Clostridium difficile on the healthcare system. Clin Infect Dis 55(S2):S88–S92. https://doi.org/10.1093/cid/cis335

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lessa F, Mu Y, Bamberg W et al (2015) Burden of Clostridium difficile infection in the United States. N Engl J Med 372(9):825–834. https://doi.org/10.1056/NEJMoa1408913

    Article  CAS  PubMed  Google Scholar 

  3. Kelly C, LaMont JT (2008) Clostridium difficile — more difficult than ever. N Engl J Med 359:1932–1940

    Article  CAS  PubMed  Google Scholar 

  4. McFarland LV, Elmer GW, Surawicz CM (2002) Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol 97:1769–1775. https://doi.org/10.1016/S0002-9270(02)04195-3

    Article  CAS  PubMed  Google Scholar 

  5. McFarland LV, Surawicz CM, Greenberg RN et al (1994) A randomized placebo-controlled trial combination with standard antibiotics for Clostridium difficile disease. JAMA. 271:1913–1918

    Article  CAS  PubMed  Google Scholar 

  6. Kassam Z, Lee CH, Yuan Y, Hunt RH (2013) Fecal microbiota transplantation for clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 108(4):500–508. https://doi.org/10.1038/ajg.2013.59

    Article  PubMed  Google Scholar 

  7. Li Y, Cai H, Wang Z, Xu J, Fang J (2016) Systematic review with meta-analysis: long-term outcomes of faecal microbiota transplantation for Clostridium difficile infection. Aliment Pharmacol Ther 43:445–457. https://doi.org/10.1111/apt.13492

    Article  PubMed  Google Scholar 

  8. Lee CH, Belanger JE, Kassam Z et al (2014) The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur J Clin Microbiol Infect Dis 33(8):1425–1428. https://doi.org/10.1007/s10096-014-2088-9

    Article  CAS  PubMed  Google Scholar 

  9. Girotra M, Garg S, Anand R, Song Y (2016) Fecal microbiota transplantation for recurrent Clostridium difficile infection in the elderly: long-term outcomes and microbiota changes. Dig Dis Sci 61(10):3007–3015. https://doi.org/10.1007/s10620-016-4229-8

    Article  PubMed  Google Scholar 

  10. Brandt LJ, Aroniadis OC, Mellow M et al (2012) Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 107:1079–1087. https://doi.org/10.1038/ajg.2012.60

    Article  PubMed  Google Scholar 

  11. Mamo Y, Woodworth M, Sitchenko K, Dhere T, Kraft C (2017) Durability and long-term clinical outcomes of fecal microbiota transplant (FMT) treatment in patients with recurrent C. difficile infection. Open Forum Infect Dis 4(Suppl 1):S384–S385

    Article  PubMed Central  Google Scholar 

  12. Fischer M, Phelps E, Bolla R, Storm M, Allegretti JR (2016) Long-term risk of Clostridium difficile infection recurrence with or without antibiotic exposure following successful fecal microbiota transplant. Gastroenterology. 150:S23. https://doi.org/10.1016/S0016-5085(16)30204-9

    Article  Google Scholar 

  13. Aroniadis OC, Brandt LJ, Greenberg A et al (2015) Long-term follow-up study of fecal microbiota transplantation for severe and/or complicated Clostridium difficile infection. J Clin Gastroenterol 50(5):1. https://doi.org/10.1097/MCG.0000000000000374

    Article  Google Scholar 

  14. Goldenberg JZ, Yap C, Lytvyn L et al (2017) Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 12:CD006095. https://doi.org/10.1002/14651858.CD006095.pub4

    Article  PubMed  Google Scholar 

  15. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 444(7122):1027–1031. https://doi.org/10.1038/nature05414

    Article  PubMed  Google Scholar 

  16. Ridaura VK, Faith JJ, Rey FE et al (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science (80- ) 341:1241214. https://doi.org/10.1126/science.1241214

    Article  CAS  Google Scholar 

  17. Alang N, Kelly CR (2015) Weight gain after fecal microbiota transplantation. Ofid. 2(Suppl 1):1–8. https://doi.org/10.1093/ofid/ofv004

    Article  Google Scholar 

  18. Wang S, Xu M, Wang W et al (2016) Systematic review: adverse events of fecal microbiota transplantation. PLoS One 11(8):1–24. https://doi.org/10.1371/journal.pone.0161174

    CAS  Article  Google Scholar 

  19. Baxter M, Colville A (2016) Adverse events in faecal microbiota transplant: a review of the literature. J Hosp Infect 92(2):117–127. https://doi.org/10.1016/j.jhin.2015.10.024

    Article  CAS  PubMed  Google Scholar 

  20. Qazi T, Amaratunga T, Barnes EL, Fischer M, Kassam Z, Allegretti JR (2017) The risk of inflammatory bowel disease flares after fecal microbiota transplantation: systematic review and meta-analysis. Gut Microbes 8(6):574–588. https://doi.org/10.1080/19490976.2017.1353848

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wadhwa A, AlNahhas M, Dierkhising R et al (2016) High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection. Aliment Pharmacol Ther 44(6):576–582. https://doi.org/10.1002/nbm.3369.Three

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Christine H. Lee.

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Conflict of interest

CL received grants from Physicians Services Incorporated, Canadian Institutes of Health Research, Rebiotix and Seres Therapeutics to conduct fecal microbiota transplant trials. JC, KH, SRJ, YP, CG, and PK have no conflicts to declare.

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This study was approved by the Hamilton Integrated Research Ethics Board. An informed consent was obtained from eligible participants prior to distributing the questionnaire.

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Lee, C.H., Chai, J., Hammond, K. et al. Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure. Eur J Clin Microbiol Infect Dis 38, 1731–1735 (2019). https://doi.org/10.1007/s10096-019-03602-2

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  • DOI: https://doi.org/10.1007/s10096-019-03602-2

Keywords

  • Long-term follow-up
  • Fecal microbiota transplantation
  • Recurrent Clostridioides difficile infection