Fecal Microbial Transplantation (Voiceover)
Fecal microbial transplantation (FMT) is an age-old technique described as early as the 4th century AD in the literature. The widespread occurrence of clostridium difficile and its increasing resistance to the existing antibiotics have necessitated the need for alternative treatments. Recently this therapy has gained popularity because it is perceived as being more natural. Many centers do not perform this procedure owing to the lack of specific guidelines outlining the process. Therefore, in this educational video, we describe the entire process in a simple step-by-step fashion as performed in our institution.
Indications for treatment pertain to 3 groups of patients. The first group are those with relapsing or recurrent CDC as defined as greater than 3 episodes of mild to moderate CDC with failure to respond to a 6 to 8 week tapering vancomycin course with or without alternative antibiotics such as metronidazole, rifaximin, or fidaxomicin or at least 2 episodes of CDC resulting in hospitalization and significant mortality. The second group are those with moderate CDC with no response to standard therapy (vancomycin or fidaxomicin) for at least 1 week, and the last group are those with severe and fulminating CDC.
The most important limiting factor of the process is the donor stool collection owing to the paucity of stool banks and the unusual nature of the transplantation. The donor can be either an intimate family member or an unrelated healthy volunteer.
Since fecal microbial transplantation does carry a potential risk for transmission of infectious agents, rigorous testing is routinely recommended. These minimal tests should be done within 4 weeks of donation. The stool tests that are usually done include looking for Clostridium Difficile toxin B, Ova and parasite examinations and routine culture for enteric pathogens. Serologic tests include Hepatitis A IgM, Hepatitis B Surface Ag, Antibodies to Hepatitis C, RPR, HIV 1 and 2 enzyme immunoassay.
Varying routes of administration are available.
- Nasogastric or nasoenteric tube;
- Upper endoscopy with duodenal infusion.
- Colonoscopy
- Flexible sigmoidoscopy
- Enema
Here we are opening a zip lock bag delivered by the donor. Inside is the sealable plastic container that has the actual stool specimen. The donor has sterilized this container at home with alcohol prior to its use.
The equipment needed includes (Figure 1 and video) a dedicated blender; a simple kitchen blender will do. At this step we are removing the donor stool that is still sealed in the container. We have normal saline solution, which will be used as a diluent. Make sure it has no added antimicrobial agents. We have spatulas that are used in stirring. Some institutions use coffee filters as a final staining. We use colanders for filtering. One is a coarse colander and one that is a finer mesh. Here are 10 syringes that will be used to collect the final specimen. We are opening the donor stool container. Between 50 to 60 grams of stool have been recommended to be mixed with 300 cc of normal saline. In our institution we traditionally use larger amounts than this. In this case we are mixing the stool with a liter of normal saline because we plan to divide this donor specimen into three different fecal transplants on this particular day. Here we begin pouring the saline into the blender (Figure 2) in preparation for emulsifying the stool. In other institutions, water and even milk has been used as diluents. The emulsified stool is then removed from the blender and poured through the first colander (Figure 3). This is the coarse colander, which removes large particulate matter that could cause obstruction in the channel of the endoscope. In this stage we begin the second filtering process using a smaller meshed colander which is a finer sieve. The liquid is poured through and the spatula can again be used to help remove the liquid. At this point coffee filters can also be used if finer filtration is needed. The final product should appear as a blenderized liquid solution, and this brown liquid has been shown to be very rich in gut microbes. The filtered donor solution is now being drawn up into individual 60 cc syringes to be used in the fecal microbial transplant. We typically use one syringe of 60cc for duodenal infusion either via the upper endoscope or nasoduodenal tube. For colonoscopic instillation we use ten 60 cc syringes; 400cc are placed in the terminal ileum and 600 cc into the right side of the colon. The filtration process is now complete and the donor specimen can be moved from preparation area to the endoscopy suite.
This first patient is having an instillation into the proximal small bowel via pediatric colonoscope. At the point the endoscope is advanced well past the stomach. Here we are in the jejunum and we take the 60 cc syringe with the donated filtered fecal material and instill it (Figure 4). After instillation the procedure should be quickly terminated pausing only to remove excess air from the stomach to avoid the risk of nausea, vomiting and aspiration.
Here we are doing a second case where the specimen is being instilled via the colonoscope. The colonoscopy is proceeded to the point where we reach the right side of the colon. The patient is placed in the right side down position so any fluid instilled will stay on the right side of the colon. The IC valve is entered and the first 400 cc is placed in the terminal ileum. Here we are completing the instillation of the fluid into the terminal ileum. The endoscope is withdrawn quickly into the cecum. Here is a view of the cecum containing the fluid (Figure 5 and video). The patient is still in the right side down position. After instillation the procedure should be terminated rather quickly. Try to remove the instrument very quickly to avoid suctioning any of the fluid or displacing it to the left side of the colon. All examination of the colon including biopsies should have been done on insertion. Therefore this is not always a very good screening colonoscopy.
Adverse events may occur including gastrointestinal symptoms such as bloating, flatulence, nausea, abdominal pains and or cramps and diarrhea. These are mild and self-limiting. Aspiration due to duodenal instillation and sedation at the time of colonoscopy. Possible flare up or transient fever in patients with underlying inflammatory bowel disease.
In summaryFMT is a simple and effective treatment for patients with recurrent CDC. The idea of altering intestinal microbiome is a novel concept, and establishing standardized protocols will go a long way in making the therapy more accessible to the masses. However, there are still unanswered questions regarding the long-term effects and potential transmission of infectious agents and diseases that are caused by the gut microbial changes. Moving forward further studies are required to improve our understanding of this complex mechanism.