Fecal Transplantation a Feasible Antibiotic Alternative for C. Difficile Treatment

ichael Bretthauer, MD, PhD

In a proof-of-concept trial published in the New England Journal of Medicine, researchers have found that fecal microbiota transplantation (FMT) is a feasible treatment alternative to antibiotic therapy in patients with a primary Clostridium difficile infection, with no differences between the 2 strategies in regard to overall treatment response or treatment-related adverse events.

“The advantages of FMT are the avoidance of antibiotics, which are associated with side effects, high costs, and antibiotic resistance,” study author Michael Bretthauer, MD, PhD, of Oslo University, told MD Magazine®. “Thus, reduction in antibiotic usage is of high importance for individual patients and society.”

A total of 20 patients with an acute C. difficile infection were randomized to either fecal microbiota transplantation (n=9) or oral metronidazole (n=11). The definition of C. difficile in this study included presentation with ≥3 loose stools/day and a positive stool test for C. difficile. Patients randomized to fecal microbiota transplantation received 1 enema comprised of 60ml of anaerobically cultivated human intestinal microbiota, whereas patients taking antibiotic therapy received a regimen consisting of an oral 400 mg dose of metronidazole 3 times per day for 10 days.

Clinical cure, which was defined as achieving ≤3 bowel movements per day or stools that were firm in consistency as well as having no evidence of C. difficile recurrence at day 70, comprised the primary endpoint. Patients who met the definition for the primary endpoint were characterized as having achieved a full primary response. Patients characterized as achieving a full secondary response were individuals who had been provided additional therapy to meet the primary endpoint but who did not experience infection recurrence during follow-up.

Fecal microbiota transplantation and antibiotic therapy were associated with similar rates of patients achieving a full primary response (56% [95% CI 21-86] vs 45% [95% CI 17-77], respectively; P = 1.00). A full secondary response was observed in 2 of 4 patients in the FMT group who received additional antibiotic therapy 4 days after treatment initiation.

Among the remaining 6 patients randomized to antibiotic therapy, none had achieved a full secondary response, primarily due to either a refractory of recurrent infection. Overall response to treatment was similar between the FMT (78% [95% CI 40-97]) and antibiotic group (45% [95% CI 17-77) during the study period (P = .20).

Limitations of this analysis, according to Bretthauer, include the fact that it’s a pilot study and features a small number of participants. “Although the study’s results with regard to efficacy and safety of FMT for treatment of primary C. difficile infection are very promising, the treatment should be tested in a larger phase III trial before implementation in clinical practice,” Bretthauer concluded.

The authors note that a phase 3 trial is currently underway which is examining the effects associated with FMT as a primary C. difficile infection treatment. The study includes patients with ≥2 C. difficile infection recurrences who have failed standard oral metronidazole and/or oral vancomycin therapy.

The study, “Fecal Microbiota Transplantation for Primary Clostridium difficile Infection,” was published as a letter to the editor of the New England Journal of Medicine.