Editors' ChoiceMicrobiome

You Want To Give Me WHAT?

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Science Translational Medicine  13 Feb 2013:
Vol. 5, Issue 172, pp. 172ec30
DOI: 10.1126/scitranslmed.3005832

The development of antibiotic-resistant bacteria has been widely publicized, but another negative consequence of the widespread use of broad spectrum antibiotics has received less attention: the growing prevalence and virulence of Clostridium difficile enterocolitis. When the normal intestinal flora is obliterated by antibiotics, C. difficile can take over, causing manifestations ranging from watery diarrhea to toxic mega-colon, sepsis, and death. Decades ago, physicians tried using donor feces to treat antibiotic-refractory C. difficile disease, with the goal of restoring the normal bowel flora and with some reports of success; however, this practice has not caught on for a variety of reasons, including the aversive nature of feces. Although antibiotics directed at C. difficile are usually effective, an increasing number of patients have recurrent disease resistant to standard antibiotic therapy—hence, the idea of using donor feces has resurfaced.

van Nood and colleagues now report a randomized controlled trial of donor feces infusion for vancomycin-refractory C. difficile colitis. Patients were randomized to one of three groups: (i) short-course vancomycin treatment and bowel lavage followed by duodenal infusion of donor feces, (ii) vancomycin treatment alone, or (iii) vancomycin treatment plus bowel lavage. The donor feces were administered fresh, diluted in saline, strained, and screened for common stool- and bloodborne pathogens. The trial was designed to enroll 120 patients but stopped early after the enrollment of 43 patients because of the striking difference in the cure rate: 15 of 16 patients (94%) were cured in the donor feces group, compared with 31% in the vancomycin group and 23% in the vancomycin plus lavage group. Analysis of the bacterial flora in patients before and after administration of the donor feces demonstrated that the infusion was effective in reestablishing a diverse gut microbiome.

Although the results of this trial are striking, several limitations must be noted. For one, several important groups of patients that commonly develop severe C. difficile colitis were excluded, including immunocompromised patients, critically ill patients, and patients who were on antibiotics for other infections. Second, the trial was not blinded. Third, the control groups had already demonstrated antibiotic-resistant disease and therefore may have been randomized to treatments that were likely to fail. In addition, it remains unclear whether carefully mixed cultures of bacteria might substitute for stool administration. Nevertheless, this study emphasizes the importance of the human microbiome in the maintenance of health and treatment of disease and opens the door to a new therapeutic option for a deadly and increasingly common pathogen—that is, if we can get over our natural aversion to using excrement as medicine.

E. van Nood et al., Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J .Med. 368, 407-415 (2013). [Abstract]

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