Evolution of Targeted Therapies for C difficile

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Evolution of Targeted Therapies for C difficile
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Sahil Khanna, MBBS, MS, FACG, AGAF

Click to view more from Gastroenterology Data Trends 2023. 

References
  1. Di Bella S et al. Toxins (Basel). 2016;8(5):134. doi:10.3390/toxins8050134
  2. Turner NA, Anderson DJ. Clin Colon Rectal Surg. 2020;33(2):98-108. doi:10.1055/s-0040-1701234
  3. Czepiel J et al. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221. doi:10.1007/s10096-019-03539-6
  4. Sekirov I et al. Gut microbiota in health and disease. Physiol Rev. 2012;90(3):859-904. doi:10.1152/physrev.00045.2009
  5. Posteraro B et al. Expert Opin Biol Ther. 2018;18(4):469-476. doi:10.1080/14712598.2018.1452908
  6. Khanna S. J Intern Med. 2021;290(2):294-309. doi:10.1111/joim.13290
  7. Seekatz AM et al . Therap Adv Gastroenterol. 2022;15:17562848221134396. doi:10.1177/17562848221134396
  8. Federal Drug Administration. FDA approves first fecal microbiota product: Rebyota approved for the prevention of recurrence of Clostridioides difficile infection in adults [press release]. Published November 30, 2022. Accessed July 14, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product
  9. Bafeta A et al. Ann Intern Med. 2017;167(1):34-39. doi:10.7326/M16-2810
  10. Guh AY et al; Emerging Infections Program Clostridioides difficile Infection Working Group. N Engl J Med. 2020;382(14):1320-1330. doi:10.1056/NEJMoa1910215
  11. Centers for Disease Control and Prevention. What is C. diff? Last reviewed September 7, 2022. Accessed July 14, 2023. https://www.cdc.gov/cdiff/what-is.html
  12. Centers for Disease Control and Prevention. Patients and families: be antibiotics aware. C. diff infection—Am I at risk? Accessed July 14, 2023. https://www.cdc.gov/cdiff/pdf/FS-Cdiff-PatientsFamilies-508.pdf
  13. Centers for Disease Control and Prevention. 2019 annual report for the emerging infections program for Clostridioides difficile infection. Last reviewed February 1, 2023. Accessed July 14, 2023. https://www.cdc.gov/hai/eip/Annual-CDI-Report-2019.html
  14. Kelly CR et al. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
  15. Tariq R et al. Therap Adv Gastroenterol. 2021;14:1756284821994046. doi:10.1177/1756284821994046
  16. McDonald LC et al. Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
  17. Wilcox MH et al. N Engl J Med. 2017;376(4):305-317. doi:10.1056/NEJMoa1602615
  18. Guilleman MM et al. Gene Ther. 2023;30:455-462. doi:10.1038/s41434-021-00236-y
  19. Sims MD et al; ECOSPOR IV Investigators. JAMA Netw Open. 2023;6(2):e2255758. doi:10.1001/jamanetworkopen.2022.55758
  20. Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD2). ClinicalTrials.gov identifier: NCT02299570. Updated January 2021. Accessed August 2023. https://classic.clinicaltrials.gov/ct2/show/results/NCT02299570
  21. Khanna S et al. Clin Infect Dis. 2021;73(7):e1613-e1620. doi:10.1093/cid/ciaa1430
Author and Disclosure Information

Professor of Medicine
Chair GI Hospital Practice
Associate Program Director, Internal Medicine Residency Program
Medical Director Desk and Secretarial Operations
Mayo Clinic
Rochester, Minnesota

Publications
GI and Hepatology News
Author(s)
Sahil Khanna, MBBS, MS, FACG, AGAF
Author(s)
Sahil Khanna, MBBS, MS, FACG, AGAF
Author and Disclosure Information

Professor of Medicine
Chair GI Hospital Practice
Associate Program Director, Internal Medicine Residency Program
Medical Director Desk and Secretarial Operations
Mayo Clinic
Rochester, Minnesota

Author and Disclosure Information

Professor of Medicine
Chair GI Hospital Practice
Associate Program Director, Internal Medicine Residency Program
Medical Director Desk and Secretarial Operations
Mayo Clinic
Rochester, Minnesota

Click to view more from Gastroenterology Data Trends 2023. 

Click to view more from Gastroenterology Data Trends 2023. 

References
  1. Di Bella S et al. Toxins (Basel). 2016;8(5):134. doi:10.3390/toxins8050134
  2. Turner NA, Anderson DJ. Clin Colon Rectal Surg. 2020;33(2):98-108. doi:10.1055/s-0040-1701234
  3. Czepiel J et al. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221. doi:10.1007/s10096-019-03539-6
  4. Sekirov I et al. Gut microbiota in health and disease. Physiol Rev. 2012;90(3):859-904. doi:10.1152/physrev.00045.2009
  5. Posteraro B et al. Expert Opin Biol Ther. 2018;18(4):469-476. doi:10.1080/14712598.2018.1452908
  6. Khanna S. J Intern Med. 2021;290(2):294-309. doi:10.1111/joim.13290
  7. Seekatz AM et al . Therap Adv Gastroenterol. 2022;15:17562848221134396. doi:10.1177/17562848221134396
  8. Federal Drug Administration. FDA approves first fecal microbiota product: Rebyota approved for the prevention of recurrence of Clostridioides difficile infection in adults [press release]. Published November 30, 2022. Accessed July 14, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product
  9. Bafeta A et al. Ann Intern Med. 2017;167(1):34-39. doi:10.7326/M16-2810
  10. Guh AY et al; Emerging Infections Program Clostridioides difficile Infection Working Group. N Engl J Med. 2020;382(14):1320-1330. doi:10.1056/NEJMoa1910215
  11. Centers for Disease Control and Prevention. What is C. diff? Last reviewed September 7, 2022. Accessed July 14, 2023. https://www.cdc.gov/cdiff/what-is.html
  12. Centers for Disease Control and Prevention. Patients and families: be antibiotics aware. C. diff infection—Am I at risk? Accessed July 14, 2023. https://www.cdc.gov/cdiff/pdf/FS-Cdiff-PatientsFamilies-508.pdf
  13. Centers for Disease Control and Prevention. 2019 annual report for the emerging infections program for Clostridioides difficile infection. Last reviewed February 1, 2023. Accessed July 14, 2023. https://www.cdc.gov/hai/eip/Annual-CDI-Report-2019.html
  14. Kelly CR et al. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
  15. Tariq R et al. Therap Adv Gastroenterol. 2021;14:1756284821994046. doi:10.1177/1756284821994046
  16. McDonald LC et al. Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
  17. Wilcox MH et al. N Engl J Med. 2017;376(4):305-317. doi:10.1056/NEJMoa1602615
  18. Guilleman MM et al. Gene Ther. 2023;30:455-462. doi:10.1038/s41434-021-00236-y
  19. Sims MD et al; ECOSPOR IV Investigators. JAMA Netw Open. 2023;6(2):e2255758. doi:10.1001/jamanetworkopen.2022.55758
  20. Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD2). ClinicalTrials.gov identifier: NCT02299570. Updated January 2021. Accessed August 2023. https://classic.clinicaltrials.gov/ct2/show/results/NCT02299570
  21. Khanna S et al. Clin Infect Dis. 2021;73(7):e1613-e1620. doi:10.1093/cid/ciaa1430
References
  1. Di Bella S et al. Toxins (Basel). 2016;8(5):134. doi:10.3390/toxins8050134
  2. Turner NA, Anderson DJ. Clin Colon Rectal Surg. 2020;33(2):98-108. doi:10.1055/s-0040-1701234
  3. Czepiel J et al. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221. doi:10.1007/s10096-019-03539-6
  4. Sekirov I et al. Gut microbiota in health and disease. Physiol Rev. 2012;90(3):859-904. doi:10.1152/physrev.00045.2009
  5. Posteraro B et al. Expert Opin Biol Ther. 2018;18(4):469-476. doi:10.1080/14712598.2018.1452908
  6. Khanna S. J Intern Med. 2021;290(2):294-309. doi:10.1111/joim.13290
  7. Seekatz AM et al . Therap Adv Gastroenterol. 2022;15:17562848221134396. doi:10.1177/17562848221134396
  8. Federal Drug Administration. FDA approves first fecal microbiota product: Rebyota approved for the prevention of recurrence of Clostridioides difficile infection in adults [press release]. Published November 30, 2022. Accessed July 14, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product
  9. Bafeta A et al. Ann Intern Med. 2017;167(1):34-39. doi:10.7326/M16-2810
  10. Guh AY et al; Emerging Infections Program Clostridioides difficile Infection Working Group. N Engl J Med. 2020;382(14):1320-1330. doi:10.1056/NEJMoa1910215
  11. Centers for Disease Control and Prevention. What is C. diff? Last reviewed September 7, 2022. Accessed July 14, 2023. https://www.cdc.gov/cdiff/what-is.html
  12. Centers for Disease Control and Prevention. Patients and families: be antibiotics aware. C. diff infection—Am I at risk? Accessed July 14, 2023. https://www.cdc.gov/cdiff/pdf/FS-Cdiff-PatientsFamilies-508.pdf
  13. Centers for Disease Control and Prevention. 2019 annual report for the emerging infections program for Clostridioides difficile infection. Last reviewed February 1, 2023. Accessed July 14, 2023. https://www.cdc.gov/hai/eip/Annual-CDI-Report-2019.html
  14. Kelly CR et al. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
  15. Tariq R et al. Therap Adv Gastroenterol. 2021;14:1756284821994046. doi:10.1177/1756284821994046
  16. McDonald LC et al. Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
  17. Wilcox MH et al. N Engl J Med. 2017;376(4):305-317. doi:10.1056/NEJMoa1602615
  18. Guilleman MM et al. Gene Ther. 2023;30:455-462. doi:10.1038/s41434-021-00236-y
  19. Sims MD et al; ECOSPOR IV Investigators. JAMA Netw Open. 2023;6(2):e2255758. doi:10.1001/jamanetworkopen.2022.55758
  20. Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD2). ClinicalTrials.gov identifier: NCT02299570. Updated January 2021. Accessed August 2023. https://classic.clinicaltrials.gov/ct2/show/results/NCT02299570
  21. Khanna S et al. Clin Infect Dis. 2021;73(7):e1613-e1620. doi:10.1093/cid/ciaa1430
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Clostridioides difficile (C difficile) is a gram-positive anaerobic bacillus that produces toxins (enterotoxin A [TcdA] and cytotoxin B [TcdB]) that can damage the lining of the gastrointestinal tract and cause potentially life-threatening disease of the large intestine.1C difficile infection (CDI) is not only a common nosocomial infection, but an increasing incidence is seen in the community with a high disease burden, as reinfection often occurs.2 C difficile is very contagious and spreads easily via contaminated surfaces that act as reservoirs (especially in healthcare settings); the spores of this bacterium are very hard to kill.3

CDI often occurs either while the patient is taking antibiotics or soon after finishing them, as the intestinal (gut) microbiome and metabolism are altered, which allows for C difficile to proliferate.4 People with a compromised immune system or other comorbid conditions, or who are older than 65 years of age, are especially prone to CDI.1

Antibiotics are the first-line treatment for primary and recurrent CDI (rCDI), although they do not always kill the spores,3 and the dysbiosis caused by antibiotics within the gut environment still needs to be addressed.4 A humanized monoclonal antibody (an immunoglobulin G against the cytotoxin B), in combination with antibiotics, has been shown to help prevent rCDI in a subset of patients.5

Therapies that help restore the gut microbiota to a eubiotic state, especially after antibiotic treatment for C difficile, have been shown to help manage and prevent future rCDI. Experimental fecal microbiota transplantatio (FMT) performed under enforcement discretion from the FDA is one such microbiota restoration therapy.3 Microbes harvested from healthy donor stool are transplanted into the intestine of a recipient (usually via colonoscopy) to help restore the gut microbiome and prevent CDI.7

Two therapeutics are approved by the FDA for prevention of rCDI. The first one was approved in 2022 and is a rectal administration product derived from human donor stool (fecal microbiota live-jslm [Rebyota]).8 The other is an oral capsule (fecal microbiota spores live-bprk [Vowst]) containing live spores from fecal microbiota.6 With these exciting advances, we can now begin to address additional unmet needs with future research into microbiota restoration therapies.9

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