By Carol A. Kemper, MD, FACP
Clinical Associate Professor of Medicine, Stanford University, and Division of Infectious Diseases, Santa Clara Valley Medical Center
Dr. Kemper reports no financial relationships relevant to this field of study.
SOURCES: Drekonja D, et al. Fecal microbiota transplantation for Clostridium difficile infection. A systemic review. Ann Intern Med 2015;12:630-638.
Surawicz CM. Fecal microbiota transplantation: What we know and what we need to know. Ann Intern Med 2015;162;662-663.
Relapsing and refractory Clostridium difficile infection (CDI) has become a real challenge for clinicians and affected patients alike. Some patients wind up in a seemingly never-ending cycle of illness, gradual improvement, followed by a prolonged vancomycin taper, and eventual relapse. Relapse occurs in 15-30% of patients following an initial (successfully treated) episode, and further relapse occurs in > 50% of those with second or subsequent episodes. Reports of successful resolution of this nasty infection using fecal microbiota transplantation (FMT) has generated enthusiasm. But available studies vary in their approach, their timing, the frequency of treatment (single dose vs multiple doses over several days), and several guidelines now have been proposed for screening of potential donors. Some recommend FMT for those with two or more episodes, whereas the American College of Gastroenterology suggests FMT can be considered in those with three or more episodes.
Researchers performed a systematic review of the available literature related to FMT. Two randomized, controlled trials, 28 case series, and five case reports were identified for a total of 561 FMT subjects. Combining the results of the two randomized clinical trials, 27 of 36 patients treated with FMT had resolution of symptoms (75%). One of these studies administered material via nasogastric (NG) tubes, with successful resolution of symptoms in 81% at 3 months. In contrast, < 30% of patients in the two comparator arms receiving vancomycin treatment or vancomycin lavage had sustained resolution of symptoms at 3 months. In the first study, FMT was administered following 4-5 days of orally administered vancomycin (500 mg four times daily). Interestingly, 8 of the 43 patients included in this study were enrolled after their first episode of CDI. In the second randomized, controlled study, FMT was administered via NG vs colonoscopy in 20 patients, with resolution of symptoms in 60% vs 80% (P = 0.63). FMT was administered 3 days following completion of anti-CDI treatment.
In the various case series, researchers performed FMT in 480 patients with a history of 3-12 relapses over a 3-27 month period. Although none of these studies included a comparator arm, 85% reportedly remained disease-free following administration of FMT. In addition to these, there were seven smaller non-comparator studies for patients with refractory CDI, all using various methods, with an overall resolution rate of 55%. Symptomatic improvement was observed in 0-100%.
A third randomized, controlled trial, not published in time to be included in this analysis, demonstrated successful resolution of symptoms in 90% of patients treated with FMT vs 26% in a vancomycin treatment group; researchers ended the study prematurely because of this substantial difference in favor of FMT.
In conclusion, FMT appears effective in approximately 55-90% of patients with relapsing and refractory CDI, and will prove a blessing to those who have been in a miserable cycle of recurrent disease. Observed side effects were minimal and included complaints of cramping, bloating, nausea, transient fever, and dizziness. One patient receiving FMT through a misplaced NG tube developed pneumoperitoneum and polymicrobial bacteremia.
Many questions remain, including who, what, and how. Various protocols are used to screen donors, and methods for administration of FMT differ. For those without access to stool, one company is marketing frozen stool from pre-screened healthy donors. I’ve had several enterprising patients who have tried various approaches, including small home tap water enemas mixed with stool (strained to remove the peas and carrots), to capsules stuffed with a spouse’s stool, kept refrigerated, and swallowed the day following completion of orally administered vancomycin. A couple of patients have tried 10 capsules twice a day for 1-2 days, one of whom relapsed a week later, and tried it again with success. While expressing initial reluctance, patients were quick to embrace this approach following yet another relapse. One of the randomized, controlled trials above indicated that patients were initially squeamish, but when contacted 3 months later, 97% said they would do it again.
It’s amazing that such a simple procedure — administration of a small amount of fecal material — can effect such an important change in your bowel flora. But that is how we develop our flora, with ingestion of fecal material from the world around us, bit by bit. As one of my favorite instructors is fond of saying, “Think of the world as covered by a thin layer of feces.”