Donor feces infusion for first episode of Clostridium difficile infection in patients at risk for recurrent infection

Clostridium difficile is the most common cause of antibiotic-associated
diarrhea. Because of more virulent strains and evolving
antimicrobial resistance, incidence, outbreaks, mortality, and recurrent CDI
have increased in the past decade.
Unfortunately, about 25% of patients with CDI experience recurrent disease;
this proportion rises to 70% in patients with
multiple recurrences. The most important cause of recurrent CDI is persistent
disruption of the intestinal microbiota. Patients
with recurrent CDI can be cured with FMT (defined as the transfer of intestinal
microbiota from a healthy donor), which restores
the healthy microbiota. Using a clinical prediction rule, patients at risk
(>35%) for recurrent CDI can be identified.
To date, studies on FMT have focused on treatment of recurrent CDI. The aim of
our study is to investigate the potential benefit
of FMT after antibiotic treatment to prevent all recurrences of CDI in patients
at high risk (35%-45%) of treatment failure.
Prevention of recurrent CDI is the most effective way to reduce morbidity,
mortality and health care costs.

Recently the Netherlands National Donor Feces Bank (NNDFB) was founded to
facilitate FMT and to standardize the protocol,
which will lead to cheaper, safer and wider availability of this new treatment
approach. The NNDFB aims to provide hospitals
with screened, frozen material ready for clinical use. We propose to
investigate the use of FMT with frozen suspensions
provided by the NNDFB as treatment of a first episode of CDI in a randomized
controlled trial.

The primary objective of this study is to investigate whether FMT after
antibiotic therapy is more effective than conventional
antibiotic therapy alone in patients with a first episode of CDI.

Our study is designed as a monocenter, open label, randomized trial comparing
donor feces infusion (223 ml) preceded by 10 days vancomycin (250 mg q.i.d.)
and bowel lavage (1 liters Moviprep® or 2 liters KleanPrep®) to 10 days of
vancomycin (250 mg orally q.i.d.). Patients will be randomly allocated at 1:1
ratio to the two treatment options.

Duodenal infusion of donor feces (provided by the NNDFB), after a 10-day course
of vancomycin (250 mg orally q.i.d.) with
bowel lavage one day prior to FMT.

Full colon lavage and insertion of nasoduodenal tube could cause inconveniency.
Studies which evaluated donor feces infusion against recurrent CDI reported no
serious adverse events directly related to donor feces infusion. Main side
effects of donor feces infusion are diarrhea, cramping, belching, nausea,
abdominal pain, and dizziness, which resolve within a few days.
Participating patients are asked to collect fecal samples before and after FMT.
Patients will have brief scheduled telephone contacts at 1 week, 2 weeks, 4
weeks, and 6 weeks after FMT to discuss recovery and presence of recurrence or
adverse events.

Overall success rate of donor feces infusion against CDI has been proven to be
90%. However, no data is available with regard to an initial episode of CDI.
The biggest benefits of donor feces infusion are restoring the gut microbiota
and the possibility of eradication of C. difficile without exposure to
antibiotics. The use of antibiotics like vancomycin does not restore the gut
microbiota. Long term effects of FMT are still unknown.