FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI
FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI
The purpose of the study is to determine the safety and efficacy of Fecal Microbiota
 Transplant (FMT) for the treatment of the recurrence of Clostridium difficile infection (CDI)
 as compared to standard antibiotic therapy. Patients who have tested positive for CDI within
 90 days of an admission for relapse of CDI will be approached to participate in this
 open-label, randomized controlled trial. Patients will either be randomized to the
 intervention group (receive FMT via retention enema) or the control group (receive
 antimicrobials targeting CDI).
This trial is an open-label, randomized, controlled trial evaluating the safety and efficacy
 of fecal microbiota transplantation (FMT) for the treatment of the recurrence of Clostridium
 difficile infection (CDI) as compared to standard antibiotic therapy. Clostridium difficile
 infection (CDI) has increased in incidence and severity over the last decade and is
 associated with poor outcomes including increased morbidity, mortality, and healthcare costs
 (1-8). Relapse occurs in 15-35% of patients after the first episode of CDI and 45-65% of
 patients who have one relapse will experience a subsequent relapse (9, 10). Dysbiosis -
 decreased diversity of the fecal microbiome - is thought to contribute to the high rate of
 relapse (11). FMT quickly and successfully restores normal intestinal microorganisms of the
 diseased patient via infusion of a liquid stool preparation from a healthy donor. FMT
 resulted in disease resolution in ~90% of cases reported in a systematic review and
 meta-analyses without any significant adverse events noted (12, 13).

 All hospitalized patients in the NorthShore system >18 years of age who are diagnosed with
 active CDI, defined as >3 diarrheal stools per day and a positive C. difficile polymerase
 chain reaction (PCR) assay, will be evaluated for inclusion in the study. Hospitalized
 patients presenting with their first or greater relapse of CDI occurring between 15 and 90
 days after an index episode of CDI will be eligible for enrollment. Exclusion criteria will
 include pregnancy, neutropenia (absolute neutrophil count <1000/μl), contraindication for
 retention enema, or food allergy not controlled for in the donor diet. Eligible patients will
 undergo written informed consent followed by randomization into intervention and control
 groups.

 Patients who are randomized to the intervention group will have antimicrobials targeting C.
 difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A
 second FMT via retention enema will be administered at 24 hours if diarrhea persists.
 Patients randomized to the control group will be treated with antimicrobials targeting C.
 difficile according to the Society for Healthcare Epidemiology of America Clinical Practice
 Guidelines for CDI (18). FMT will be offered to the control group after 90 days if they
 experience relapsing CDI.

 Two healthy "universal" donors who have previously donated fecal material for FMT have
 expressed willingness to participate in the study. Donors will complete the American
 Association of Blood Banks donor questionnaire for exposure to infectious agents as well as
 undergo serologic and stool testing for communicable diseases or pathogenic bacteria/viruses
 as previously described (17).
Inclusion Criteria:

 -  Diagnosis of active C. difficile infection, defined as > 3 diarrheal stools per day
 and a positive C. difficile PCR assay

 -  Hospitalized patient presenting with first relapse of CDI occuring between 15 and 90
 days after an index episode of CDI

 Exclusion Criteria:

 -  Pregnancy

 -  Neutropenia (absolute neutrophil count <1000/microliters)

 -  Contraindication for retention enema

 -  Food allergy not controlled in the donor diet