FMT Consistently Demonstrates Efficacy for Recurrent C. difficile Infections

Clinical trials consistently demonstrate that fecal microbiota treatment is an effective treatment strategy for recurrent CDI, yet standardization practices vary.

Sahlil Khanna, MBBS, MS

During a session at the Anaerobe Congress 2018 in Las Vegas, NV, this July, Sahil Khanna, MBBS, MS, of the Mayo Clinic presented an up-to-date review of the current literature showing the effectiveness of fecal microbiota transplant (FMT) for patients with recurrent Clostridium difficile infection (CDI).

Khanna told MD Magazine® that FMT is a highly effective treatment option for recurrent CDI.

“There are large phase 3 clinical trials which are being performed to study the effect of standardized microbiota-based therapies for recurrent CDI,” Khanna said. “There is a need to streamline identification of patients with true CDI who would benefit from FMT.”

For multiple recurrent C. difficile infections, Khanna suggested choosing FMT after antibiotic therapy and to use antibiotics plus anti-toxin B monoclonal antibody therapy. Probiotics, including Saccharomyces boulardii and kefir, are also recommended for these patients.

Currently, the efficacy of FMT for CDI is over 85%, making FMT a promising approach for affected patients. In fact, FMT tends to show superiority over oral vancomycin, Khanna noted.

Although there is no effect related to the donor on efficacy of treatment, Khanna indicated that screening and recruitment standardization is needed in clinical practice. Specifically, Khanna noted that clinical microbiome replacement is often heterogeneous in nature and lacks a standardized consensus regarding recruitment, collection, screening, and preparation.

Collection and processing of stools varies substantially across centers, according to the presented analysis by Bafeta et al in 2017.1

In a double-blind, randomized controlled trial presented at the congress, donor FMT was found to be superior to autologous FMT in regard to the percentage of patients cured without relapse.2 Additional data presented during his talk showed that the highest predictors for FMT failure in the CDI patient population include antibiotic use <8 weeks of treatment, prior hospitalizations related to CDI, underlying irritable bowel disorder, and severe and severe-complicated CDI.3-6

Standardized strategies, such as microbiota replacement, are likely to replace conventional individual donor-directed microbial replacement, Khanna added. In the phase 3 PUNCH CD III trial, RBX2660, a microbiota-based therapy, was more effective than placebo in preventing recurrent CDI.6 Additionally, SER-109, another microbiome-based therapy, demonstrated similar efficacy and an overall cure rate of 96.7% in a phase 1 trial led by Khanna.8

In addition to the studies presented during the session, Khanna also presented a hypothetical case study of a patient with CDI. He highlighted the importance of communicating to patients the value of clinical trials; however, the patient in the presented case opted for a FMT via colonoscopy following a 10-day course of vancomycin vs undergoing multiple visits in a clinical trial and the chance of being randomized to placebo.

“In future, microbiota-based therapies may be used for earlier CDI rather than waiting for 3 or more episodes,” Khanna concluded. “Additionally, defined microbial consortia should be studied for recurrent CDI.”

Disclosure: Khanna is a consultant for Facile Therapeutics, Merck and Company, Premier, Inc, Probio Tech, Rebiotix, Inc (paid to Mayo clinic), and Shire.

References:

  1. Bafeta A, Yavchitz A, Riveros C, Batista R, Ravaud P. Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review. Ann Intern Med. 2017;167(1):34-39.
  2. Kelly CR et al. Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial. Ann Intern Med. 2016;165(9):609-616.
  3. 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. 2018;66(1):134-135.
  4. Patron RL, Hartmann CA, Allen S, et al. Vancomycin Taper and Risk of Failure of Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection. Clin Infect Dis. 2017;65(7):1214-1217.
  5. Fischer M, Kao D, Mehta SR, et al. Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study. Am J Gastroenterol. 111(7):1024-1031.
  6. Tariq R, Smyrk T, Pardi DS, Tremaine WJ, Khanna S. New-Onset Microscopic Colitis in an Ulcerative Colitis Patient After Fecal Microbiota Transplantation. Am J Gastroenterol. 2016;111(5):751-752.
  7. Dubberke ER, Lee CH, Orenstein R, et al. Results from a Randomized Placebo-Controlled Clinical Trial of a RBX2660-a Microbiota-based Drug for the Prevention of Recurrent Clostridium difficile Infection [published online March 29, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy259.
  8. Khanna S, Pardi DS, Kelly CR, et al. A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection. J Infect Dis. 2016;214(2):173-181.