American Journal of Gastroenterology Lecture

Intestinal Microbiota and the Role of Fecal Microbiota Transplant (FMT) in Treatment of C. difficile Infection

Lawrence J Brandt MD; MACG


Am J Gastroenterol. 2013;108(2):177-185. 

In This Article

CDI and FMT: How to Do It

The potential for transmission of infectious agents is a major concern, however, and rigorous screening tests are recommended to reduce such risk.[21] As an integral part of our protocol for a double-blind randomized controlled trial of FMT for recurrent CDI (see below), the NIH required that donor stool be tested for C. difficile toxin, enteric bacterial pathogens (including specifically Listeria monocytogenes, Vibrio cholera and Vibrio parahemolyticus), parasites such as Giardia (Giardia antigen test) Cryptosporidium (Cryptosporidium antigen test), and Isospora (acid-fast stain), and Rotavirus; donor blood must be screened for hepatitis A (IgM), B (HBsAg, anti-HBc (IgG and IgM), and anti-HBsAg) and C (HCV antibody) viruses, human immunodeficiency virus (HIV) types 1 and 2, and syphilis. Screening for H. pylori is also prudent regardless whether FMT is performed via the upper or lower route. Recipients are tested for HIV 1 and 2, Hepatitis A, C, and syphilis. This testing is much more rigorous and extensive than that performed in the community, where most practitioners just have donor stool screened for enteric pathogens, ova and parasites, and C. difficile toxin. Of course, because of the ready availability of stool, patients may accept offers of unscreened stool from well-meaning friends and relatives who are aware of FMT. I have had several patients who wanted me to perform FMT on them after self-administration of unscreened donor stool had failed. This practice of using unscreened stool is to be eschewed, except perhaps for emergent FMT, when timing may be more critical than long-term safety outcome. As the perturbing effect of antibiotics on the intestinal microflora can persist for 3 months or more, donors are excluded if they have had antibiotics within this time; high-risk sexual behaviors, a body piercing or tattoo in the previous 3 months or recent incarceration are also exclusions. A history of diarrhea, constipation, inflammatory bowel disease, colorectal polyps or cancer, irritable bowel syndrome, immunocompromise, morbid obesity, metabolic syndrome, atopy, and chronic fatigue syndrome are additional donor exclusions because they conceivably may be transmittable by inoculation with intestinal microbiota.

One systematic review provided data to suggest that FMT using stool from a related donor (spouse, or intimate partner), yields a somewhat higher rate (93.3%) of CDI resolution than when stool from an unrelated donor (84%) was used.[28] More recent experience with frozen/thawed or fresh fecal preparations obtained from "standard" or "universal" donors, however, gave excellent results (90–92% resolution, 9% recurrence) exceeding those obtained with patient-selected donors (70% resolution, 30% recurrence), and casting doubt on preference for related or intimate contacts.[36]

So what are the "nuts and bolts" of FMT? The donor has a relatively simple job: to provide the stool in a timely fashion. This, I have seen, may cause a level of "performance anxiety" in some donors. To facilitate passage and to enable me to work with a soft stool, I have the donor take a double dose of milk of magnesia before bedtime the night before the procedure. A soft stool is passed into a clean plastic container. I add non-bacteriostatic saline to the stool, stir it, shake it, and mix it thoroughly. Others have opted for the blender method and some practitioners have even had patients bring their own blender. Obviously, if a blender is to be used for several patients, its parts would have to be sterilized before the next procedure. Some authors use milk as the suspending fluid, others water; saline and milk may give slightly lower resolution (86.2 and 88.6%, respectively) and recurrence (3.0 and 3.2%, respectively) rates, while water may give higher resolution (98.5%) and recurrence (7.8%) rates.[28] The amount of stool to use has not been standardized, although those given to weighing and measuring rather than just "eyeballing" the product's appearance favor 50 g in 250 cc of diluent. It seems as if more is better and most "FMTers" are now using about 300 cc for colonic FMT and 60 cc for upper tract FMT. An administered volume of < 200 ml gave a resolution rate of 80% and a relapse rate of 6.2%, whereas a volume of >500 ml gave a resolution rate of 97.3% and a relapse rate of 4.7%. Use of < 50 g of stool was associated with resolution and relapse rates of 8.2% and 3.8%, respectively, whereas >50 g of stool had resolution and relapse rates of 86.2% and 1.0%, respectively.[28] I like to use donor stool within 8 h of passage although this time limit has never been studied rigorously. Stool should not be frozen and need not, but may, be refrigerated for travel. After adding my beverage of choice to the stool and getting it to the proper consistency, I filter the mixture through gauze pads to remove large particulate matter that may obstruct the colonoscope's channel and then draw the elixir into 60 cc catheter-tipped syringes. It is recommended that stool preparation be performed under a hood, because stool is rated as a Level 2 biohazard, although this recommendation is not practical and this is the safest stool we, as gastroenterologists, will ever encounter. Recipients should take a large volume colon lavage before the procedure, regardless of which route is chosen. In cases of recurrent CDI, I have the patients stop their vancomycin and other antibiotics 3 days before the procedure if possible; this too has not been studied against continuing the antibiotics up until or even after the procedure. I also have the recipient take two loperamide tablets before they leave home or about an hour before the procedure to help them hold the administered stool for at least 4 h, and preferably 6 h, after FMT. To actually do the transplant, I perform a colonoscopy and upon reaching the cecum, I remove the accessory channel cap of the colonoscope, connect a piece of suction tubing to it, and then administer one syringe-full of stool suspension after another into the cecum/ascending colon or into the ileum until the desired amount has been given. I have on many occasions taken random colon biopsy specimens during insertion to ascertain histology without adverse effect. After infusion of the donor stool, I withdraw swiftly, aspirating air only from the distal left colon, sigmoid and rectum for patient comfort.