FMT for Moderate to Severe CDI: A Randomised Study With Concurrent Stool Microbiota Assessment

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Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness, associated with significant morbidity and mortality and has a high burden on health-care system. The incidence of CDI has increased to epidemic proportion worldwide over the past decade. Communi...

Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness, associated with significant morbidity and mortality and has a high burden on health-care system. The incidence of CDI has increased to epidemic proportion worldwide over the past decade. Community-acquired CDI, elderly and hospitalized patients receiving antibiotics are the main group at risk for developing CDI 1. Currently, the first-line treatment for C. difficile-associated diarrhea includes cessation of the antibiotic implicated in the development of CDI, treatment with metronidazole or vancomycin and recently Fidaxomicin which is yet to be available in Hong Kong2. However, disease recurrence is an increasing problem and 20% to 60% of patients experience at least one recurrence within a few weeks of completion of antibiotic treatment. Moreover, an increasing number of patients who require life-saving emergency colectomy experience persistent CDI after surgery. Until recently, an effective treatment against recurrent CDI is not available. Generally, repeated and extended courses of vancomycin are prescribed3. Fecal microbiota transplantation (FMT) defined as infusion of feces from healthy donors to affected subjects has attracted great interest in recent years and is now recommended as the most effective therapy for CDI not responding to standard therapies 4. Systematic reviews of prospective trials, case series and one randomized controlled trial have shown an overall cure rate of close to 100% 5, 6. More than 50% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur 7. While FMT has been proven to be effective in refractory CDI, the role of FMT as first-line therapy in a subset of patients with severe CDI, or high risk features for severe CDI has not been studied. These are generally patients in whom the risk of colectomy and mortality is exceedingly high. In addition, the mechanism of FMT in CDI is not completely clear, and limited data are available on the effects of FMT on the microbiota post FMT. It has been suggested that CDI results in deficiencies in fecal flora composition, particularly of Bacteroides and Firmicutes, and these deficiencies in the microbiota facilitate colonization with C. difficile. Microarray analysis in small number of subjects has shown a major shift in the patients' microbiota after donor-feces infusion toward that of the donors8. The experimental tools required for in depth analysis of the intestinal microbiota are now becoming available. This study aims to investigate the efficacy of FMT as first line therapy in patients with moderate to severe CDI and to assess changes in the fecal microbiota after FMT using pyrosequencing techniques.

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