Spotlight on fecal microbiota transplantation

Two recent studies focused on fecal microbiota transplantation for recurrent Clostridium difficile infection, while a third examined the utility of anaerobic preparations in patients with mild to moderately active ulcerative colitis.

One recent study found adverse effects of antibiotic use after successful fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI), a second found that FMT plus vancomycin worked better than fidaxomicin or vancomycin alone for recurrent CDI, and a third found promising results of using anaerobically prepared donor stool to induce remission in patients with ulcerative colitis.

In the first study, researchers enrolled 404 patients (mean age, 61.3 years; 63% women) who had FMT for recurrent CDI at three large FMT referral centers in the U.S. and Canada. They assessed participants' antibiotic use, as well as concomitant use of prophylactic anti-CDI antibiotics or probiotics, and evaluated time to CDI recurrence after FMT. Results were published online on Jan. 10 by Digestive Diseases and Sciences.

Over a mean follow-up of 18.1 ± 11.9 months (range, 2.2 to 45.2 months) after FMT, 33 (8.1%) participants had a recurrence of CDI. Of the 111 (27.4%) participants who had used a non-CDI antibiotic, 18 (16.2%) experienced recurrence of the infection. Participants who used non-CDI antibiotics were more likely to develop CDI compared to those who did not (hazard ratio, 8.44; P<0.001). The risk of recurrence did not differ between patients who received anti-CDI antibiotic prophylaxis and those who did not (hazard ratio, 1.88; P=0.200), and probiotic prophylaxis was associated with a greater risk of recurrence (hazard ratio, 2.65; P=0.045).

Limitations of the study include its retrospective design and lack of randomization, the study authors noted. “While we are awaiting future prospective studies … we found that the prophylactic use of anti-CDI antibiotics or probiotics was not protective at preventing CDI in patients after successful FMT,” they concluded.

In the second study, a single-center randomized trial, researchers compared the effects of FMT plus vancomycin with those of fidaxomicin or vancomycin alone for treatment of recurrent CDI. They enrolled 64 consecutive adults with recurrent CDI at a gastroenterology clinic in Denmark. Patients were randomized to receive FMT by colonoscopy or nasojejunal tube after four to 10 days of vancomycin (125 mg four times daily; n=24), to receive 10 days of fidaxomicin (200 mg twice daily; n=24), or to receive 10 days of vancomycin (125 mg four times daily; n=16).

The primary outcome was a combination of clinical resolution and a negative result from a polymerase chain reaction test for C. difficile toxin eight weeks following treatment. Results were published online on Jan. 2 by Gastroenterology.

Overall, 17 (71%) patients who received FMT plus vancomycin achieved clinical resolution and negative C. difficile test results, compared to eight (33%) patients given fidaxomicin and three (19%) patients given vancomycin (P=0.009 for FMT vs. fidaxomicin; P=0.001 for FMT vs. vancomycin; and P=0.310 for fidaxomicin vs. vancomycin).

Limitations of the study include the absence of patients infected with C. difficile ribotype 027, so the results may not be generalizable to settings with a high frequency of ribotype 027, the study authors noted. In addition, the study interventions were unblinded, and therefore observer bias may have affected reporting, they said. “Resolution rates similar to that in patients randomized to FMT were found in patients who had been randomized to antibiotic treatment and were offered rescue FMT following CDI recurrence and in patients who could not be randomized and were offered FMT off protocol,” they noted.

In the third and final study, researchers conducted a preliminary randomized, double-blind trial at three Australian tertiary referral centers to assess the efficacy of a short duration of FMT therapy using anaerobically prepared stool to induce remission in patients with ulcerative colitis. They randomized 73 adults (mean age, 39 years; 45% women) with mild to moderately active ulcerative colitis to receive either a three-dose, one-week course of treatment with anaerobically prepared pooled donor FMT (n=38) or autologous FMT (n=35) through colonoscopy followed by two enemas over seven days.

Patients were followed for 12 months, and autologous FMT participants were offered open-label therapy at eight weeks. Researchers assessed the primary outcome, steroid-free remission of ulcerative colitis (defined as a total Mayo score of ≤2, with an endoscopic Mayo score of ≤1), at week 8. At 12 months, they reassessed steroid-free remission. Results were published online on Jan. 15 by JAMA.

Overall, 69 (95%) patients completed the trial. Twelve of the 38 (32%) participants who received pooled donor FMT achieved steroid-free remission at week 8, compared with three of the 35 (9%) who received autologous FMT (difference, 23% [95% CI, 4% to 42%]; odds ratio, 5.0; P=0.030). Five of the 12 (42%) participants who received donor FMT and achieved remission at week 8 maintained remission at 12 months. There were three serious adverse events in the donor FMT group (worsening colitis, C. difficile colitis requiring colectomy, and pneumonia) and two in the autologous FMT group (both worsening colitis).

The study's limitations include the fact that 12-month data are limited by the crossover, open-label design and are therefore observational, the authors noted. They added that there was a substantial loss to follow-up at 12 months and that there was no antibiotic washout period prior to study entry, which may have biased the initial microbiome assessment.

“Given the signal of benefit seen so far, larger multicenter trials are an important next step and should be designed to answer questions about FMT delivery methods, mechanisms of action, and long-term durability of effects,” an accompanying editorial noted.