FMT Versus Antimicrobials for Initial Treatment of Recurrent 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 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