TORONTO - Fecal transplants cure most cases of persistent C. difficile infection, a landmark study has shown.
That comes as no surprise to the increasing numbers of people who have turned to this unorthodox treatment for relief from the debilitating condition.
But this publication marks the first time a randomized controlled trial — the most reliable type of study — has shown that the treatment is effective.
"Overall I think this paper is an important paper to say that performing fecal transplants does work," said Dr. Tom Louie, an infection prevention and control expert in Calgary who has performed more than 100 fecal transplants. He was not involved in this study.
"It will lead us to the tipping point where ... people may be more aware of the value of the normal bowel flora. This is verification that good bugs help."
The study is published Wednesday in the New England Journal of Medicine, one of the most prestigious medical journals in the world. It was done by researchers from the Netherlands.
Fecal transplants, first performed in the late 1950s, have come to be regarded by many as the current best chance for cure for people with persistent, recurrent C. difficile.
The idea is relatively simple: Use the feces of a healthy person to restore the normal mix of bacteria to a gut that has been ravaged by C. difficile.
But generating the data to prove that the procedure works as well as people like Louie believe has been difficult.
Getting institutional and ethics board approvals to conduct this type of experiment has been tough. And where once doctors had a hard time talking people into taking the treatment, now patients who have battled C. difficile often don't want to run the risk they will be randomly assigned not to get the procedure in a clinical trial. They want the fecal transplant.
Researchers in Toronto are conducting a randomized controlled trial on a different version of the same procedure, but have had trouble finding patients who will agree to take part for that very reason.
In the Dutch trial, the researchers had to promise the patients that if they were randomly assigned to get antibiotics rather than a fecal transplant, they could have the procedure after the trial ended if they still needed it, said senior author Dr. Josbert Keller.
"That was the only way we could enrol patients," he said in an interview from the Hague, where he is a gastroenterologist at Haga Teaching Hospital.
"Most people think that patients are reluctant receiving this treatment. But those patients who have relapsed like four or five times, they are just desperate. It's a terrible disease for them with an increased mortality. It just hampers the whole life."
The team used a tube snaked from a nostril down into the duodenum — the top of the small intestine — to deliver the fecal material to the patients' intestinal tracts.
The feces came from donors who had been screened to make sure they didn't have HIV or a number of other infectious diseases. The stools were mixed with saline, stirred and then allowed to sit. Later the fluid was separated from the solids and only the fluid was used in the procedure.
A half-litre of the fluid was dripped into the intestines via the tube. On the day of the procedure most of the patients had diarrhea and some had stomach cramping. But by the next day, most were cured.
In fact, the study was stopped early when it became clear that fecal transplants were far superior to the alternatives the procedure was tested against: the antibiotic vancomycin, which is the standard treatment for C. difficile diarrhea; or a treatment called bowel lavage — a cleansing of the bowel, like the preparation for a colonoscopy — followed by vancomycin.
Of 16 patients who received a fecal transplant, 13 were cured after a single treatment. Two of the remaining three were cured after a second transplant from a different donor, for an overall cure rate of 94 per cent.
Only four of 13 patients (31 per cent) who received vancomycin were cured; three of 13 (23 per cent) who had the bowel lavage followed by vancomycin were cured.
After the trial was completed, 18 people who were not cured by the antibiotic had fecal transplants and 11 were cured on the first try. An additional four were cured after a second transplant.
The approach Keller and his colleagues used — delivering the transplant via a nose tube — is not the only way to do this procedure. Other clinicians use a sort of reverse colonoscopy approach or a reverse enema. People who use these other procedures report cure rates in the 90 per cent range as well.
Dr. Andrew Simor, head microbiologist at Toronto's Sunnybrook Health Sciences Centre, said some might feel that the Dutch study cannot be extrapolated to cover the other approaches too.
"My own feeling ... combining these results with previous cases series (of patients) I would think that either route ought to be adequate," Simor said.
While the results are welcome, and should signal that this approach can be safely used in recurrent C. difficile cases, Simor suggested there are still hurdles ahead.
Health systems don't have billing codes for this procedure. And hospitals may struggle to figure out how to process donor stool.
Even Keller admitted that while this procedure works and is a good option for the moment, better alternatives would be preferable.
Figuring out what is needed to restore the bacterial balance destroyed by C. difficile may allow scientists to devise a targeted transplant — a probiotic treatment, perhaps — that would have the same effect without exposing a patient to someone else's stool.
"We shouldn't believe this is the best we can give," Keller said. "We should give better treatments in the future."