Since its discovery as the cause of pseudomembranous colitis in 1978, Clostridium difficile (C.
difficile) has become an increasingly important pathogen. Initially, C.
difficile infection (CDI)
was largely confined to patients with healthcare exposure; however, it is now also affecting those
with no or limited contact with the healthcare system. In 2013, the U.S. Centers for Disease
Control and Prevention placed C.
difficile into its top threat category of "urgent" in its first threat
report on antimicrobial resistance.
A major challenge in treating CDI is the high rate of recurrent disease. Recurrence occurs in
15-30% of patients, and among those with a single episode of recurrence, the risk of further
recurrence increases after each episode. Multiple treatment/recurrence episodes can result in
repeated hospitalizations, clinic visits, deconditioning, malnourishment, and fecal continence
issues. These effects are debilitating, contribute to decreased quality of life and prolonged
courses of antimicrobial treatment and rarely can be fatal. Antimicrobial treatment for these
episodes of recurrent disease yields reported success rates between 30% and 80%, depending
on the number of recurrences, and on the agent and duration of treatment selected. These suboptimal
response rates have helped spur the investigation of additional therapeutic options
including fecal microbiota transplantation (FMT) for the treatment of CDI.
CDI is characterized by severe alterations in the colonic microbiome (normal colonic bacteria).
Restoring the normal microbiome has been proposed as a method for preventing recurrence. The
most widely utilized intervention has been probiotics yet these products provide only a limited
number and diversity of microorganisms. Fecal microbiota transplantation is increasingly utilized
as a treatment for patients with recurrent CDI; based on the idea that to restore all the organisms
that comprise the normal colonic flora, simply import the colonic microbiome of a healthy
person. FMT has been performed in hundreds of patients, with outcomes from more than 500
cases reported in the medical literature - most in non-controlled case series. Reported success
rates of up to 100% and the recent publication of a randomized controlled trial (RCT) comparing
FMT to antimicrobial treatment have increased interest in the procedure.
The key questions for the review were:
Key Question #1: What is the effectiveness of fecal microbiota transplantation for recurrent CDI compared to
standard therapy? Does effectiveness vary by method of transplantation?
Key Question #2: What is the effectiveness of fecal microbiota transplantation for refractory CDI compared
to standard therapy? Does effectiveness vary by method of transplantation?
Key Question #3: What is the effectiveness of fecal microbiota transplantation as initial therapy for CDI
compared to standard therapy? Does effectiveness vary by method of transplantation?
Key Question #4: What are the harms of fecal microbiota transplantation therapy compared to standard
therapy for initial, recurrent, or refractory CDI? Do the harms vary by method of transplantation?
Key Question #5: Is the procedure acceptable to patients? Does patient acceptability vary by method of