Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection

  • Yuying LuoEmail author
  • Aimee L. Lucas
  • Ari M. Grinspan
Original Article



Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving.


To elucidate the most cost-effective strategy for managing recurrent CDI.


A decision tree analysis was created from a modified third-party payer’s perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed.


Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost–effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy.


FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.


Cost-effectiveness Recurrent Clostridioides difficile infections Fecal microbiota transplants Bezlotoxumab 


Author's contribution

AMG serves as the guarantor of the article. All authors contributed to the inception, design, and research of the study. All authors approved the final version of the manuscript.

Compliance with Ethical Standards

Conflicts of interest

Ari M. Grinspan has received lecture fees and honorarium from Merck.


  1. 1.
    Sheitoyan-Pesant C, Abou Chakra CN, Pepin J, Marcil-Heguy A, Naul V, Valiquette L. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. Clin Infect Dis. 2016;62:574–580.CrossRefGoogle Scholar
  2. 2.
    Zhang S, Palazuelos-Munoz S, Balsells EM, Nair H, Chit A, Kyaw MH. Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. BMC Infect Dis. 2016;16:447.CrossRefGoogle Scholar
  3. 3.
    McDonald LC, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Accessed 1 Dec 2018.
  4. 4.
    Ianiro G, Maida M, Burisch J, et al. Efficacy of different faecal microbiota transplantation protocols for Clostridium difficile infection: a systematic review and meta-analysis. United Eur Gastroenterol J. 2018;6:1232–1244.CrossRefGoogle Scholar
  5. 5.
    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;318:1985–1993.CrossRefGoogle Scholar
  6. 6.
    Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305–317.CrossRefGoogle Scholar
  7. 7.
    Le P, Nghiem VT, Mullen PD, Deshpande A. Cost-effectiveness of competing treatment strategies for Clostridium difficile infection: a systematic review. Infect Control Hosp Epidemiol. 2018;39:412–424.CrossRefGoogle Scholar
  8. 8.
    Rajasingham R, Enns EA, Khoruts A, Vaugh BP. Cost-effectiveness of treatment regimens for Clostridioides difficile infection: an evaluation of the 2018 Infectious Diseases Society of America guidelines. Clin Infect Dis. 2019. Scholar
  9. 9.
    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;58:1507–1514.CrossRefGoogle Scholar
  10. 10.
    Varier RU, Biltaji E, Smith KJ, et al. Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection. Infect Control Hosp Epidemiol. 2015;36:438–444.CrossRefGoogle Scholar
  11. 11.
    Baro E, Galperine T, Denies F, et al. Cost-effectiveness analysis of five competing strategies for the management of multiple recurrent community-onset Clostridium difficile infection in France. PLoS One. 2017;12:e0170258.CrossRefGoogle Scholar
  12. 12.
    Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment and prevention of Clostridium difficile infections. Accessed 1 Dec 2018.
  13. 13.
    Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2006;145:758–764.CrossRefGoogle Scholar
  14. 14.
    Lam SW, Neuner EA, Fraser TG, Delgado D, Chalfin DB. Cost-effectiveness of three different strategies for the treatment of first recurrent Clostridium difficile infection diagnosed in a community setting. Infect Control Hosp Epidemiol. 2018;39:924–930.CrossRefGoogle Scholar
  15. 15.
    Cammarota G, Ianiro G, Gasbarrini A. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol. 2014;48:693–702.CrossRefGoogle Scholar
  16. 16.
    Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165:609–616.CrossRefGoogle Scholar
  17. 17.
    Gold MR, Franks P, McCoy KI, Fryback DG. Toward consistency in cost-utility analyses: using national measures to create condition-specific values. Med Care. 1998;36:778–792.CrossRefGoogle Scholar
  18. 18.
    Youngster I, Mahabamunge J, Systrom H, et al. Oral, frozen fecal microbiota transplantation for recurrent Clostridium difficile infection. BMC. 2016;13:134.Google Scholar
  19. 19.
    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.CrossRefGoogle Scholar
  20. 20.
    Stranges PM, Hutton DW, Collins CD. Cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the treatment of Clostridium difficile infection in the United States. Value Health. 2013;16:297–304.CrossRefGoogle Scholar
  21. 21.
    Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55:S154–S161.CrossRefGoogle Scholar
  22. 22.
    Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015;41:835–843.CrossRefGoogle Scholar
  23. 23.
    Hota SS, Sales V, Tomlinson G, et al. Oral Vancomycin followed by fecal transplantation versus tapering oral vancomycin treatment for recurrent Clostridium difficile infection: an open-label, randomized controlled trial. Clin Infect Dis. 2017;64:265–271.CrossRefGoogle Scholar
  24. 24.
    Louie TJ, Miller MA, Mullane KM, et al. OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–431.CrossRefGoogle Scholar
  25. 25.
    Crawshaw BP, Chien H, Augestad KM, Delaney CP. Effect of laparoscopic surgery on health care utilization and costs in patients who undergo colectomy. JAMA Surg. 2015;150:410–415.CrossRefGoogle Scholar
  26. 26.
    McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol. 2002;97:1769–1775.CrossRefGoogle Scholar
  27. 27.
    Bhangu A, Nepogodiev D, Gupta A, et al. Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium difficile colitis. Br J Surg. 2012;99:1501–1513.CrossRefGoogle Scholar
  28. 28.
    Hensgens MP, Goorhuis A, Dekkers OM, et al. All-cause and disease specific mortality in hospitalized patients with Clostridium difficile infection: a multicenter cohort study. Clin Infect Dis. 2013;56:1108–1116.CrossRefGoogle Scholar
  29. 29.
    OpenBiome. FMT Preparation Information. Accessed 12 July 2019.
  30. 30.
    Micromedex Red Book [online database]. Truven Health Analytics website. Accessed 12 July 2019.
  31. 31.
    Lamontagne F, Labbe A-C, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg. 2007;245:267–272.CrossRefGoogle Scholar
  32. 32.
    Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235:363–372.CrossRefGoogle Scholar
  33. 33.
    Tengs TO, Wallace A. One thousand health-related quality-of-life estimates. Med Care. 2000;38:583–637.CrossRefGoogle Scholar
  34. 34.
    Stouthard M, Essink-Bot M, Bonsel G, Barendregt J, Kramers P. Disability weights for diseases in the Netherlands. Department of Public Health. Erasmus University Rotterdam; 1997.Google Scholar
  35. 35.
    Finch Therapeutics. Efficacy, safety, and tolerability study of oral full-spectrum microbiotaTM (CP101) in Subjects with Recurrent C. Diff (PRISM3). NLM identifier: NCT03110133. Accessed 1 Jan 2019.
  36. 36.
    Rebiotix Inc. Microbiota restoration therapy for recurrent Clostridium difficile infection (PUNCHCD3). NLM identifier: NCT03244644. Accessed 1 Jan 2019.
  37. 37.
    Vedanta Biosciences. Randomized phase 2 study of VE303 for prevention of recurrent Clostridium difficile infection (CONSORTIUM). NLM identifier: NCT03788434. Accessed 1 Jan 2019.
  38. 38.
    Seres Therapeutics. ECOSPOR III - SER-109 versus placebo in the treatment of adults with recurrent Clostridium difficile infection (ECOSPORIII). NLM identified: NCT03183128. Accessed 1 Jan 2019.
  39. 39.
    Fischer M, Allegretti J, Smith M, et al. A multi-center, cluster randomized dose finding Study of fecal microbiota transplantation capsules for recurrent Clostridium difficile infection. United Eur Gastroenterol J. 2015;3:561–571.CrossRefGoogle Scholar
  40. 40.
    Prabhu VS, Dubberke ER, Dorr MB, et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018;66:355–362.CrossRefGoogle Scholar
  41. 41.
    Zellmer C, De Wolfe TJ, Van Hoff S, et al. Patient perspectives on fecal microbiota transplantation for Clostridium difficile infection. Infect Dis Ther. 2016;5:155–164.CrossRefGoogle Scholar
  42. 42.
    Guery B, Menichetti F, Veli-Jukka A, et al. Extended-pulse fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND). Lancet Infect Dis. 2018;18:296–307.CrossRefGoogle Scholar
  43. 43.
    Cozar-Llisto A, Ramos-Martinez A, Cobo J. Clostridium difficile infection in special high risk populations. Infect Dis Ther. 2016;5:253–269.CrossRefGoogle Scholar
  44. 44.
    Garey KW, Aitken SL, Gschwind L, et al. Development and validation of Clostridium difficile health-related quality-of-life questionnaire. J Clin Gastroenterol. 2017;50:631–637.CrossRefGoogle Scholar
  45. 45.
    FDA. FDA warns about potential risk of serious infections caused by multi-drug resistant organisms related to the investigational use of fecal microbiota for transplantation. Accessed 24 July 2019.
  46. 46.
    AGA. Fecal microbiota transplant national registry. NLM identified: NCT03325855. Accessed 1 Jan 2019.
  47. 47.
    El-Matary W. Fecal microbiota transplantation: long-term safety issues. Am J Gastroenterol. 2013;108:1537–1538.CrossRefGoogle Scholar
  48. 48.
    Panchal P, Budree S, Scheeler A, et al. Scaling safe access to fecal microbiota transplantation: past, present, future. Curr Gastroenterol Rep. 2018;20:15.CrossRefGoogle Scholar
  49. 49.
    Way A, Atkins K, Kao D. Cost averted with timely fecal microbiota transplantation in the management of recurrent Clostridium difficile infection in Alberta, Canada. J Clin Gastroenterol. 2016;50:747–753.CrossRefGoogle Scholar
  50. 50.
    Merlo G, Graves N, Brain D, et al. Economic evaluation of evaluation of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection in Australia. J Gastoenterol Heptaol. 2016;31:1927–1932.CrossRefGoogle Scholar
  51. 51.
    Juul FE, Garborg K, Bretthauer M, et al. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018;378:2535–2536.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MedicineThe Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.The Henry D. Janowitz Division of GastroenterologyThe Icahn School of Medicine at Mount SinaiNew YorkUSA

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