Fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection

INTRODUCTION

The gut flora is probably the most important first-line host defense against pathogen colonization via mechanisms involving resistance to flora colonization and the mucosal immune system. "Colonization resistance" involves the production of antimicrobial factors, competition for nutrients in the matrix and binding sites on the epithelium by resident flora [1]. The gut flora also educates and primes the mucosal immune response to discriminate between the maintenance of homeostasis with commensal flora on one hand and the requirement to eliminate the offending pathogen on the other [2]. The combined complex host-microbe interactive system involving the controlling effect of gut flora on the epithelium, the immune system and the other intestinal components including mucosal vascularity, lymphoid tissue mass and peristalsis, has been described as a "virtual organ" [2]. The integrity of each of these components is crucial to host defense and survival.

Alteration of the gut flora components, such as by the use of antimicrobial agents, can promote overgrowth with pathogenic organisms such as Clostridium difficile. (See "Epidemiology, microbiology, and pathophysiology of Clostridium difficile infection".)

Reconstitution of the gut flora by exogenous administration of probiotics offers the potential to prevent and possibly treat infection. Such an approach has traditionally involved oral administration of limited species of bacteria or yeast. However, the ability of these organisms to colonize the colonic epithelium is variable and the specific complement of microorganisms required to prevent or treat infection is unclear. Data supporting a role for oral probiotics in gastrointestinal disease including C. difficile infection have been mixed. (See "Probiotics for gastrointestinal diseases".)

An alternative approach involves administration of the entire fecal flora from a healthy individual, an approach referred to as fecal bacteriotherapy. Although the data are limited to case series, fecal bacteriotherapy has been used successfully to treat relapsing C. difficile infection and more recently for refractory inflammatory bowel disease [3]. Relapse of C. difficile occurs in 10 to 25 percent of patients treated with metronidazole or vancomycin. Furthermore, multiple relapses in the same patient are common, and up to 10 or more bouts of relapsing colitis have occurred in some patients. (See "Treatment of antibiotic-associated diarrhea caused by Clostridium difficile".)

While promising, relatively few patients have been treated, and this approach has not yet been standardized. Furthermore, concern related to transmission of infectious agents and an aversion to the nature of this therapy have hampered its further development [4]. This topic review will summarize the rationale and experience with fecal bacteriotherapy in the treatment of C. difficile infection.