- In a prospective registry study of 272 patients with recurrent or refractory Clostridium difficile infection (rCDI), the majority achieved cure with fecal microbiota transplant (FMT)
- Many patients achieved cure with one dose of FMT (15 capsules on each of two consecutive days)
- Cirrhotic and noncirrhotic patients were equally likely to achieve cure
- The need for two or three doses of FMT was 10 times more likely in patients with cirrhosis than in those without
- Based on these study findings, Massachusetts General Hospital now considers 40 to 60 FMT capsules initially to treat rCDI in patients with cirrhosis
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Fecal microbiota transplant (FMT) is an established therapy for recurrent or refractory Clostridium difficile infection (rCDI) in noncirrhotic patients. However, there has been minimal evidence that it can correct the intestinal microbial dysbiosis that often accompanies cirrhosis.
Now, in a prospective registry study, Patricia L. Pringle Bloom, MD, fellow with the Division of Gastroenterology at Massachusetts General Hospital, Elizabeth Hohmann, MD, staff physician in the Infectious Diseases Division, Raymond Chung, MD, director of Hepatology and the Liver Center, and colleagues have demonstrated that FMT often cures rCDI in patients who have cirrhosis, although such patients tend to require more doses. Their report appears in Clinical Gastroenterology and Hepatology.
This study reviewed 272 patients enrolled in a prospective registry between July 2013 and December 2017. They had at least three mild-to-moderate episodes of CDI, two episodes requiring hospitalization or a single episode of rCDI (still hospitalized after seven days of vancomycin). Their median age was 65 (range, 7–99).
Each dose of frozen FMT was administered as 15 capsules on each of two consecutive days. Patients with CDI recurrence, defined as diarrhea after 72 hours and a positive stool C. difficile test, were retreated with four to 14 days of CDI antibiotic therapy and were offered another FMT dose, up to three doses per patient.
Mass General researchers previously described their procedures in JAMA for screening donors and formulating the capsules.
Rates of Cure
Cure was defined as survival at eight weeks, while off CDI antibiotics and with no recurrence of CDI. 83% of patients achieved cure with one FMT dose, 11% required two or three doses and 6% were not cured and did not pursue additional doses because of critical illness, death or preference.
Five percent of the 272 patients had cirrhosis with Model for End-Stage Liver Disease scores of seven to 26 (median, 13). Cirrhotic and noncirrhotic patients were equally likely to achieve cure with FMT (93% vs. 94%; P = .84). No special safety concerns were identified in patients with cirrhosis.
Need for Additional Doses
Patients who required two or three FMT doses to achieve cure were significantly more likely than those who required one dose to have cirrhosis, use lactulose, use a proton pump inhibitor or have a history of prior fidaxomicin treatment.
On multivariate logistic regression analysis, only the presence of cirrhosis predicted the need for two or three doses of FMT to achieve cure. When controlling for lactulose use, the need for additional doses was 10 times more likely in patients with cirrhosis than in those without.
A Change in Practice
It may be that the intestinal microbial dysbiosis in patients with cirrhosis makes CDI refractory or impairs donor microbiota engraftment, leading to the frequent requirement for additional doses of FMT. Dysbiosis progresses with advancing cirrhosis severity.
Based on these study findings, Mass General now considers 40 to 60 FMT capsules initially to treat rCDI in patients with cirrhosis.
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