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

 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 Kong. 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 prescribed.

 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. Systematic reviews of
 prospective trials, case series and one randomized controlled trial have shown an overall
 cure rate of close to 100%. More than 50% of patients stated they would have FMT as their
 preferred first treatment option if CDI were to recur.

 This proposal aims to investigate the efficacy of FMT as first line therapy in patients with
 severe CDI and to assess changes in the fecal microbiota after FMT using pyrosequencing
 techniques.
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.
Inclusion Criteria:

 1. C. difficile infection defined as diarrhea (≥3 soft, loose or watery stools per day
 for at least 2 consecutive days or ≥8 soft or loose stools in 48 hours) and a positive
 stool test for C. difficile toxin; and

 2. Age ≥ 18; and

 3. Written informed consent obtained

 Exclusion Criteria:

 1. The presence of human immunodeficiency virus (HIV) infection with a CD4 count of less
 than 240

 2. Pregnancy

 3. GI Bleeding

 4. Acute coronary syndrome