Forget the enema bag and the tube that snakes down the throat to the intestines — the future of treatment for persistent Clostridium difficile infections may come in pill form.
A Calgary doctor who has been treating difficult-to-cure C. difficile for years with fecal transplants is reporting he has created what are in essence "poop" pills — and they do the trick.
Infectious diseases expert Dr. Tom Louie, a pioneer in the use of fecal transplants for C. difficile in Canada, has treated 27 patients with his handmade pills, and all 27 were cleared of their infections.
"They came in for lunch on an empty stomach ... and took 24 to 30 pills on average," Louie, said of the regimen, which he described to fellow scientists at the IDWeek conference in San Francisco on Thursday.
IDWeek is an annual meeting of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association and the U.S. Pediatric Infectious Diseases Society.
Louie teaches at the University of Calgary. In a telephone interview, he said he saw no side effects, and the regime was surprisingly well tolerated by patients.
"Nobody's thrown up. And nobody's complained of belly pain."
Other physicians who treat recurrent C. difficile with fecal transplants called the development good progress towards a day when there may be ready-to-use pills that can re-establish the bacterial balance for people suffering from the debilitating infection.
But they — and Louie himself — suggested this work is more a case of proving treatment in pill form can work than an immediate pivot point for the way fecal transplants for C. difficile will be administered.
That's because the pills currently used by Louie can't be mass produced and given to anyone who wants to try a fecal transplant for recurrent C. diff infection. Each patient is administered his or her own set of pills, containing bacteria from the stools of a healthy relative in most cases.
Stool processed down to bacteria
To make his capsules, Louie took stool from donors and processed the material down to just the bacteria within the stool. From between 150 and 200 grams of stool he got two to three teaspoons of concentrate, which he said had the consistency of river mud or clay, and that, diluted, was piped into capsules. Each pill was encased in three layers of gelatin capsules, to ensure they could survive the trip through the highly-acidic stomach.
"The downside of this whole study is that it is a bespoke process that you have to prepare it for each individual," explained Emma Allen-Vercoe, a microbiologist at the University of Guelph who has been working on developing a ready-to-use treatment called Repoopulate.
"I think the thing is that if you're going to take poop and process it into capsules, you need to have a specific lab that is geared up to do that. It's not the sort of thing that you can just do in your garage, you know, or even in a clinical microbiology lab," she said.
C. difficile infections can occur when people who are on antibiotics ingest spores of the bacterium. Because the antibiotics disrupt the person's normal gut flora — various bacteria that normally live harmoniously in a person's gastro-intestinal tract — C. difficile bacteria can flourish and cause persistent and lifestyle-limiting diarrhea.
While most people who develop C. difficile will be cured by strong antibiotics, some fail treatment repeatedly. It's people like that who are at their wit's end when they turn to Louie or a select number of other infectious diseases specialists in Canada and elsewhere who have been using fecal transplants to cure the infection.
They take stool from a healthy person — screened to ensure he or she is free of diseases like HIV — and mix it with saline to create a slurry. The fecal material is then transferred into the gastro-intestinal system of the patient, either using a reverse colonoscopy approach — the enema bag — or down into the stomach and intestine via a nasogastric (NG) tube inserted in a nostril.
The idea is that the fecal material from a healthy person, which is rich with normal gut bacteria, will re-establish balance in the colon of the C. diff sufferer — and in many cases it does. Doctors who perform the procedure report very high cure rates.
But some physicians and hospitals have been squeamish about doing the procedure, said Dr. Michael Silverman, of Lakeridge Health, a hospital in Oshawa, Ont., who does fecal transplants.
He says contrary to what one might expect, patients themselves are well beyond "the ick factor" by the time they come to him. Weeks or longer spent tethered to a toilet have that effect, he suggested.
"There will be some patients who will find the other things too icky and will be willing to do this. But from my experience, almost everybody goes along with the NG tube or the enema because they're past the icky phase, the patients," said Silverman.
Randomized controlled trials needed
"The patients, by the time they have multiple recurrences of diarrhea, are willing to do anything to make this not happen again."
Silverman said Louie's pill treatment would be a "nice additional option" but he doesn't anticipate all practitioners will move away from the nasogastric tube or reverse enema delivery any time soon.
"Because not everybody's going to have the ability to set up to start manufacturing capsules on site. And it's got to be on site, because the donor's on site. And it's got to be done fresh. So it can't be mass produced and shipped all over, at least at this point," he said.
But Allen-Vercoe sees this as a step towards a more final answer — a bacterial cocktail that could be produced, stored and administered in a consistent and timely way.
Louie said he is working with collaborators in Britain to try to determine which bacteria are key to re-establishing a healthy balance in the gut, with the aim of moving to a pill treatment that wouldn't have to be tailor-made for each patient.
"We've already talked about the idea that eventually we're going to end up looking at an artificial prep with components," he said.
But Dr. Christine Lee of St. Joseph's Hospital in Hamilton said this delivery method still needs to be more rigorously tested.
Lee, who has done scores of fecal transplants, said the capsule treatment will need to be the subject of a randomized controlled trial (RCT) — the gold standard of clinical studies.
"Because you don't know (if something really works) until you do the formal RCT," Lee said.
"Any observational study," — which is the type Louie performed — "it just looks great until you do an RCT," she said. "But if it really pans out that the pill form is effective then that would be fantastic."