An “Aesthetically Unappealing” Transplant: Fecal Microbiota
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When is stool transplant warranted for the treatment of C difficile infection?
Before proceeding, be forewarned: the topic at hand may adversely affect your aesthetics.1 What has become an effective treatment for recurrent, severe Clostridium difficile colitis2 (this is the “disgusting” part)? It is fecal microbiota transplant (FMT), or the instillation of healthy donor stool (comprised of healthy microbes) into the GI tract of a person with recurrent or severe C difficile colitis (the result of disease-producing bacteria not part of the normal flora). Since this approach may seem sensational at first glance, a background retrieved from several recent “Top Papers” will be presented.
A DESPERATE TREATMENT
First, how did we arrive at such a desperate treatment? Aren’t metronidazole and vancomycin enough? The answer is no, not all the time. Twenty-five percent of patients who respond to traditional therapy for C difficile colitis experience a recurrence (this number may be as high as 40%).1,3 Then, things may go from bad to worse. These persons are more likely to have a second recurrence (risk of 35% to 45%).1 For those with multiple recurrences, subsequent recurrence rates rise to 50% or higher!1
Recurrence rates alone do not tell the whole story. C difficile diarrhea can be fatal, its incidence is rising, and its estimated cost may exceed $1.1 billion per year.2 To add insult to injury, a more virulent strain of C difficile has emerged—this “bug” has acquired a gene deletion that has increased the volume of its potent A and B toxins.2 As a result, this strain can cause severe diarrhea.2
In 2010, the CDC issued practice guidelines for treatment of C difficile infections.2,4 An initial episode defined as mild to moderate (white blood cell count [WBC] of less than 15,000/µL) should be treated with metronidazole 500 mg orally 3 times a day for 10 to 14 days. A severe initial episode (WBC count higher than 15,000/µL or serum creatinine more than 1.5 times baseline) should be treated with vancomycin 125 mg orally 4 times a day for 10 to 14 days. First recurrences are treated as an initial episode. Second recurrences receive vancomycin in a “tapered and/or pulsed” regimen (see below). If C difficile infection is associated with hypotension, shock, ileus, or megacolon, vancomycin (oral/nasogastric tube) and metronidazole (intravenously) are given.
I was surprised to learn that FMT as an alternative to antibiotics was first performed in the late 1950s!2,5 Newer indications include recurrent C difficile infection (3 episodes associated with failure of a 6- to 8-week taper of vancomycin that may be accompanied by rifaximin or nitazoxanide); mild to moderate C difficile colitis not responsive to a week of therapy; severe or fulminant C difficile colitis not responsive to traditional therapy after 48 hours.2 Preferred donors should be “intimate” with the recipient (spouse or other household member) and not have other transmissible illnesses (e.g., HIV infection, hepatitis), illicit drug use, or high-risk sexual behaviors; for more disqualifiers, see reference 2.2 The transplant is given via nasogastric or nasal jejunal tubes, gastroscopy, colonoscopy (optimal), or retention enema.2 It is prepared under universal precautions, retrieved within 6 hours of the transplant, homogenized, and filtered.2
POTENTIAL NEW INDICATIONS
More indications are on the horizon. A recent paper demonstrated that duodenal infusion of donor feces is superior to standard vancomycin therapies for recurrent infection.3 Another recent article summarized potential additional benefits in an array of diseases, including ulcerative colitis, Crohn’s disease, and irritable bowel syndrome.6
Once we get past the initial shock of FMT, the procedure and salutary outcomes will become more widespread. C difficile infection is a life-threatening disease, and it appears that stool transplants will increase in frequency and enhance therapeutic success.n
REFERENCES:
1. Kelly CP. Fecal microbiota transplantation—an old therapy comes of age. N Engl J Med. 2013;368:474-475.
2. Agito MD, Atreja A, Rizk M. Fecal microbiota transplantation for recurrent C difficile infection: Ready for prime time? Cleveland Clin J Med. 2013;80:101-108.
3. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368:407-415.
4. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults. Infect Control Hosp Epidemiol. 2010;31:431-455.
5. Eiseman B, Silen W, Bascom GS, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44:854-859.
6. Brandt LJ. American Journal of Gastroenterology Lecture: Intestinal Microbiota and the Role of Fetal Microbiota Transplant in Treatment of C. difficile. Am J Gastroenterol. 2013;108:177-185.