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.