Effect of the Prebiotic Oligofructose on Relapse of Clostridium difficile-Associated Diarrhea: A Randomized, Controlled Study

Background & Aims: Ten percent to 20% of patients relapse after successful treatment of their Clostridium difficile-associated diarrhea. We set out to determine if the prebiotic oligofructose could alter the fecal bacterial flora and, in addition to antibiotic treatment, reduce the rate of relapse from C difficile infection. Methods: Consecutive inpatients with C difficile-associated diarrhea were randomly allocated to receive oligofructose or placebo for 30 days in addition to specific antibiotic treatment. Patients were followed up for an additional 30 days. The main end point was the development of further diarrhea. Stools were collected for bacterial culture and C difficile toxin measurement. Results: One hundred forty-two patients were recruited. Stool culture confirmed the probiotic effect of oligofructose with an increase in fecal bifidobacteria from baseline 8.68 log10 colony-forming units (cfu)/g to 9.37 log10 cfu/g at discharge (P < .0001; 95% confidence interval [CI], 0.45-0.94), 9.64 log10 cfu/g at 30 days (P < .0001; 95% CI, 0.74-1.18), and 9.42 log10 cfu/g at 60 days (P < .0001; 95% CI, 0.56-0.93). Thirty patients experienced a relapse of diarrhea after a median of 18 days (range, 8-34 days). Relapse of diarrhea was more common in those taking placebo (8.3% oligofructose vs 34.3% placebo, P < .001, χ2 = 14.35). Patients who relapsed stayed in the hospital longer than those who did not (53 vs 26 days, P = .021; 95% CI, 2-28), and there was a longer period of time from commencing metronidazole or vancomycin and their diarrhea settling (6 vs 3 days; P = .007; 95% CI, 1.0-5.0). Conclusions: Fecal cultures confirmed the prebiotic effect of oligofructose. Patients taking oligofructose were less likely to develop further diarrhea than those taking the placebo.