Endoscopic Fecal Microbiota Transplantation: “First-Line” Treatment for Severe Clostridium difficile Infection?

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Clostridium difficile infection (CDI) has been firmly thrust into the clinical spotlight, with the rising outbreaks of CDI in North America and Europe; emergence of the new, epidemic, hypervirulent NAP1/BI/027 strain; and markedly increased disease severity, higher colectomy rates (10.3%), and higher case-mortality rates than in decades past (34%).1–3 This strain has unique characteristics including increased production of toxin A and B, and expression of binary toxin, which contribute to these poorer outcomes.1 “Standard” treatment regimens of various antibiotics including vancomycin, metronidazole, nitazoxanide, or rifaximin, alone or in combination, fail to eradicate the infection in a proportion of patients who may go on to develop severe CDI with associated complications.4 To date, oral vancomycin and fidaxomicin are the only Food and Drug Administration-approved treatments for CDI.5 Disease recurrence is an increasing problem, with 20% to 60% of patients experiencing at least 1 recurrence within 2 to 4 weeks of completion of vancomycin treatment.6 Moreover, an increasing number of patients who require life-saving emergency colectomy experience persistent CDI postsurgery.7 There is a high and growing economic burden associated with CDI, resulting in considerable cost to patients, hospitals, national health expenditure, and insurers, with 1 report conservatively placing the cost of CDI management to the United States health care system at $1.1 billion annually.8Published reports demonstrate that patients with CDI possess deficiencies in fecal flora composition, particularly of Bacteroides and Firmicutes, most likely as a result of earlier antibiotic usage9-11 and, in some as of yet unproven manner, these deficiencies in the microbiota facilitate colonization with C. difficile. Treatment of CDI with antibiotics fail to correct these floral deficiencies; even vancomycin is a broad-spectrum antibiotic, which targets Gram-positive anaerobic and aerobic bacteria. In contrast, fecal microbiota transplantation (FMT) is a simple, inexpensive, and highly curative method of not only eradicating the CDI but also of restoring the underlying microbiotic deficiencies.12 In this editorial, we propose that endoscopic FMT be considered among the “first-line” treatments for severe CDI.Transplantation of enteric bacteria was first performed by Fabricius of Acquapendente (1537–1619) and has been reported for many decades in the veterinary literature as “transfaunation.”13 In the modern era, FMT has been performed since 195814 and has now reached the stage where it is arguably the most reliable and effective form of C. difficile eradication therapy.12,15–17 Its increasing use in clinical practice has been associated with minimal to no adverse effects.15,16,18 FMT can be performed by various routes including nasogastric (NG) tube, nasojejunal tube, upper tract endoscopy (EGD), colonoscopically or by retention enema, depending on which is deemed safest for the individual patient. However, because a single colonoscopic infusion of human fecal suspension is extremely efficacious,9,16,18,19 easy to perform, rapidly and safely accomplished, delivers the “healthy” bacteria directly to the site where the vast majority of C. difficile is established, and able to be carried out in both inpatient and outpatient settings, we propose this as the first-line treatment of CDI in the majority of patients. Moreover, colonoscopic infusion allows direct simultaneous inspection of the mucosa, and determination of preferential sites for infusing larger amounts of donor stool, for example, in areas of diverticulosis. Not only is the infusion “low-tech,” with delivery of the fecal suspension through the colonoscope biopsy channel directly into the terminal ileum or colon, but no additional training to colonoscopy is required17; it is also cost effective, without additional charge, at present, to the cost of colonoscopy. The high cure rate of FMT is unparalleled, with 90% to 100% of reported patients achieving cure.

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