Mar 102013
Fecal Transplants Cure C. difficile Infections, When Drugs Can't

Antibiotics are what cause Clostridium difficile infection to emerge in the first place, so it's perhaps no surprise that the usual treatment -- more antibiotics -- often fails. From 15-25% of patients with C. difficile are not permanently cured by their initial treatment with metronidazole, and among those whose C. diff colitis relapses, a long road of misery often awaits. Only 60% are cured after a first recurrence, with the rest requiring prolonged courses of vancomycin; in a significant proportion of patients, C. difficile persists even despite extended drug treatment. Some of these poor souls eventually undergo total colectomy -- a brutal treatment for what is theoretically a curable infection.

Transplants of human feces into the gut have anecdotally been seen to work with astounding efficacy -- a 100% cure rate in one series, among patients who had already failed drug therapies for recurrent C. diff infection. However, randomized trials were lacking. Clearly it was time for poop to make a big splash as a treatment for recurrent C. difficile -- which it did, all over the pages of the January 31, 2013 New England Journal of Medicine.

What They Did

In an open-label trial, authors randomized 43 patients with recurrent C. difficile infection at the Academic Medical Center in Amsterdam to one of three treatment arms:

  • Donor feces infusion after oral vancomycin for 4-5 days and bowel lavage with "Klean-Prep" (n=17)
  • Oral vancomycin for 4-5 days followed by "Klean-Prep" lavage (n=13)
  • Oral vancomycin 500 mg q.i.d. for 14 days (n=13)

Enemas have worked before, but infusion from above was believed to be more likely to eradicate C. difficile from the entire gut

Fifteen donors provided the stool -- an elite group recruited from over 77 candidates who were screened for illness by 53 questions and stool testing. Donors brought the stool in immediately, and it was swirled into a saline slurry and infused via nasoduodenal tube within 3 hours of defecation, on average. Among the recipients, there was no vomiting reported, thank heavens, although 20% of patients belched, according to the online supplemental appendix.

What They Found

120 patients total were planned for enrollment, but after most patients in the two control groups relapsed, and most receiving feces did not, the safety board terminated the study early for ethical reasons. In other words, doo-doo did what drugs didn't:

  • Fecal infusion cured 15 of 16 patients (94%) of recurrent C. difficile infection. 13 of 16 patients (81%) in the fecal-infusion group were cured after the first infusion of feces. Two of the remaining three were then cured with a second infusion.
  • Only 4 of 13 patients (31%) were cured by vancomycin for 14 days, and 3 of 13 (23%) by short-course vancomycin followed by bowel lavage.
  • 18 of 26 patients in the drug treatment groups had recurrences of C. difficile infection; they received off-protocol fecal infusions, and 15 were cured (83%).
What It Means

Ladies and gentlemen, we have a new and highly gross gold standard for treatment of recurrent C. difficile. Other researchers are already hard at work figuring out a way to grow the requisite colonic flora without the accompanying ick factor. One leading Canadian lab calls their stool solution RePOOPulate (no, I'm not kidding, click the link) and cultures it from stool bacteria in the "Robogut"; they describe its appearance to NPR as resembling a "vanilla milkshake." Hmm, vanilla?

So this is why dogs eat poop -- they're not degenerates, it might just be their way of staying regular. I get it now.

Els Van Nood et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med 2013; 368:407-415.

Ciaran Kelly. Fecal Microbiota Transplantation — An Old Therapy Comes of Age (NEJM Editorial)

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Hope floats: Fecal transplants cure >90% of recurrent C. difficile (RCT)