Fecal Transplant: An Investigational New Drug
Fecal Microbiota for Transplantation (FMT) is the process of placing processed stool, collected from a healthy donor, into the intestinal tract of a patient with recurrent C. difficile infection (CDI). Microbiota consists of a wide variety of bacteria, viruses, fungi, and other single-celled organisms found in the intestines and stool of healthy adults.
On June 13, 2019, the FDA release a statement about the potential risk of serious or life-threatening infections with the use of FMT:
Two sick adults with compromised immune systems (the body is unable to fight infection) received FMT
The donor stool (from one donor) and FMT recipients were not tested for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli), a multi-drug resistant organism (MDRO)
The donor stool, which was infected with ESBL-producing E.coli, infected both patients, one of which died
The gastrointestinal tract (mouth, stomach, small and large intestines) contains a highly complex community of micro-organisms (microbiota) that live and work together inside our bodies.
The human gut is estimated to contain at least one-hundred trillion bacteria and as many as 1,000 to 1,200 bacterial species, most of which reside in the colon (large intestine)
Functions of Microbiota include:
Breakdown carbohydrates for energy
Process bile: critical for digestion and absorption of fats and vitamins in the small intestine
Educate the immune system to fight against disease
Produce and secrete hormones that aid in food digestion
Competitive exclusion: resist colonization of disease-causing germs, such as C. diff
Clostridium difficile, a bacterium normally found in our intestines, can cause life-threatening diarrhea.
It is usually a side-effect of taking antibiotics, which can alter the composition of intestinal microbiota. Antibiotics work by either preventing the offending bacteria from reproducing or by killing it. Antibiotics can have a similar effect on the ‘good’ bacteria that live in our intestines
This can lead to the removal of bacteria that serve as a barrier to disease-causing germ colonization and/or persistence
Disruption of the intestinal bacteria allows competing organisms, like C. difficile, to become established in the intestinal tract, causing illness
CDI Symptoms: begin within a few days or several weeks after beginning antibiotics:
Diarrhea: loose, watery stools for several days
Loss of appetite
C. difficile can easily spread from person-to-person through direct contact with contaminated stool.
It’s estimated to cause almost half a million illnesses in the U.S. each year
About 1 in 5 patients who get C. diff will get it again.
Research has shown that within a month of diagnosis, 1 in 11 people over age 65 died of C. diff infection.
Although still considered an investigational new drug (IND), FMT is the preferred management approach for patients with CDI that is recurrent and unresponsive to antibiotic therapy. Transplantation of stool microbiota from healthy individuals can restore missing microbiota and break the cycle of CDI recurrence.
Prior to donating, all donors and their stool are tested for a comprehensive list of diseases. The stool is then blended to liquid consistency and filtered. There are four methods of delivery into the intestinal tract:
Through a tube that runs from the mouth into the small intestine
FMT has a cure rate of 80% to 90% with a single treatment. Common side effects include a mild fever and mild GI symptoms (abdominal discomfort, flatulence, diarrhea, constipation, and vomiting) that usually resolve within few weeks.