Adding fecal microbiota transplantation (FMT) to antibiotic monotherapy was superior to either fidaxomicin (Dificlir) or vancomycin alone in recurrent Clostridium difficile infection (rCDI), Danish researchers reported from a small randomized trial.
Clinical resolution and negative CDI test were achieved by 71% of FMT recipients versus 33% of fidaxomicin-only recipients, while just 19% of those given vancomycin only achieved these endpoints, according to Christian Lodberg Hvas, MD, PhD, of Aarhus University Hospital in Denmark, and colleagues.
“We found that FMT delivered by either colonoscopy or a nasojejunal tube following a short course of vancomycin was superior to both fidaxomicin and standard dose vancomycin monotherapies,” they wrote in Gastroenterology.
Rescue FMT for patients with recurrence following primary treatment as well as FMT for patients who could not be randomized yielded similar clinical results.
The investigators studied 64 consecutive rCDI patients seen at a hospital gastroenterology clinic from April 2016 to June 2018. Those who were frail, septic, or already on antibiotics were excluded. Eligible patients were randomly assigned to the following regimens: FMT via colonoscopy (79%) or tube (21%) after 4 to 10 days of vancomycin 125 mg, four times daily (FMTv, n=24), 10 days of fidaxomicin 200 mg twice daily (n=24), or 10 days of vancomycin 125 mg, four times daily (n=16).
The median age overall was 68. By gender, 83%, 69%, and 54% were female in the the three arms, respectively. Median Charlson comorbidity index scores were 2 for the vancomycin group and 1 for the two other groups. The median number of previous CDI episodes was four.
Combined clinical resolution and a negative CDI toxin test were achieved in 17 (71%, 95% CI 49-87) of 24 patients given FMTv, eight (33%, 95% CI 16-55) of 24 patients given fidaxomicin, and three (19%, C95% I 5-46) of 16 patients receiving vancomycin.
Of the 24 patients allocated to FMTv, 14 (58%, 95% CI 95% 37-78%) had no side effects. Overall, 10 patients (42%) experienced adverse events: transient abdominal pain (n=1), bloating (n=5), constipation (1), and diarrhea (n=3).
Purna C. Kashyap, MBBS, of the Mayo Clinic in Rochester, Minnesota, told MedPage Today, “This is a really interesting, well done study that further affirms the benefit of FMT in recurrent CDI. “The main take-home is that fecal transplant is better than fidaxomicin or vancomycin alone in treating recurrent CDI in patients predominantly in the outpatient setting.”
As in previous studies, the investigators did not find that donor type or route of administration made a difference, added Kashyap, who was not involved in the study.
However, he noted that since sicker and hospitalized patients were disproportionately excluded, the findings would not be as applicable to a frailer population. “But the biggest limitation is the lack of blinding, which they tried to mitigate in part by testing for CD, which provides an objective endpoint,” he stated.
The study found that a low baseline hemoglobin was the strongest and only significant predictor of FMT failure, with an odds ratio of 0.5 (95% CI 4.8-7.2) per point increase in hemoglobin. “This new finding may prove clinically relevant and could be useful for a priori identification of patients who would benefit from multiple FMT procedures,” the authors wrote. “The presence of anemia may reflect the overall burden of disease and longstanding inflammation and better reflects frailty than variables such as patient age and comorbidity.”
A 2018 meta-analysis suggested that adding a chaser of the antibiotic rifaximin (Xifaxan) after standard drugs may cut CDI relapse.
Limitations of the current study included the absence of patients infected with CD ribotype 027, which may preclude the generalizability of the findings to settings with a high frequency of this type. In addition, the study was unblinded, and observer bias may have affected reporting.
The study was funded by the Danish Regions. Hvas and co-authors disclosed no relevant relationships with industry.