Fecal transplant noninferior to vancomycin for first C. diff infection, trial finds

For patients with an initial Clostridioides difficile infection, fecal microbiota transplantation (FMT) had similar outcomes as vancomycin, suggesting it may be considered for first-line therapy, according to the authors of a recent trial.

The open-label noninferiority trial was conducted at hospitals and primary care facilities in Norway. It included 100 adults with C. difficile toxin in their stool and at least three loose stools daily who had not had a C. diff infection in the 365 days before enrollment. They were randomized to FMT without antibiotic pretreatment (n=51) or oral vancomycin, 125 mg four times daily, for 10 days (n=49). Results were published by Annals of Internal Medicine on June 17.

FMT was noninferior to vancomycin on the study's combined primary end point of clinical cure at day 14 (firm stools or less than three bowel movements daily) and no disease recurrence within 60 days: 66.7% of the FMT group achieved this versus 61.2% of the vancomycin group (difference, 5.4 percentage points [95.2% CI, −13.5 to 24.4 percentage points]; P<0.001 for noninferiority). Additional C. diff treatment was provided to 11 patients in the FMT group and four in the vancomycin group. The outcome of clinical cure at day 14 with no recurrence, with or without additional treatment, was met in 78.4% of FMT patients and 61.2% assigned to vancomycin (difference, 17.2 percentage points; 95.2% CI, −0.7 to 35.1 percentage points). The adverse event rate was similar between groups.

FMT met the predefined noninferiority threshold of a 25 percentage-point lower cure rate than vancomycin and “even showed a 5.4% numerical superiority to vancomycin, which, although not statistically significant, indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary [C. difficile infection],” said the study authors. The trial was planned to include 188 patients but the data and safety monitoring board recommended termination after the criterion for noninferiority was met in an interim analysis.

The study authors noted that optimal protocol and route for FMT have not been established but that they used enema, “a simple bedside procedure that requires minimal training and equipment, little patient burden and time, and no sedation or premedication.” Limitations of the study include its open-label design and no comparison of the interventions with fidaxomicin.

An accompanying editorial praised the study but discussed the barriers to accessing FMT in the U.S., particularly cost. “I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon, but FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome,” the editorialist wrote.