LOOKING FOR A GUT FIX
C. DIFFICILE TRIALS LOOK PROMISING
MONTREAL — Celine Edelmann was on a Buddhist retreat in a secluded cabin in northern Vermont when her intestines began to act up.
There was no phone, no electricity and no running water. “I was in the woods alone,” says the soft-spoken Montreal psychologist, who had been looking forward to the eight-day retreat, unplugged from city life.
She assumed the gut upset would pass. But after countless trips to the outhouse, Edelmann knew something was seriously wrong.
By the fifth day she was so weak she worried she wouldn’t have the strength to go for help. Edelmann packed up her things and made the 20-minute hike through the woods to the retreat’s main centre.
By nightfall, she was in isolation again — this time in a Montreal hospital being treated by nurses in protective gloves and gowns.
A virulent strain of the bacteria Clostridium difficile, or C. diff. as it’s often called, had infected and inflamed her colon. She soon found herself on a medical odyssey — with a surprising ending.
Edelmann’s illness highlights the havoc that modern life — with its clean living, refined foods and antimicrobial drugs — is wreaking on the invisible army of organisms that have co-evolved to live with, and within, humans. Antibiotics so upset the balance of her internal microbial ecosystem that she eventually was treated with a fecal transplant.
It may sound gross, but trials involving more than 300 patients — and testimonials from grateful recipients attesting to near miraculous cures — indicate fecal transplants are remarkably effective at re-establishing microbial harmony in intestines harbouring C. difficile.
C. difficile is a weedy and wily microbe that can invade the gut — with potentially deadly impact — when people take antibiotics that kill off the good, as well as the bad bacteria in the intestines.
Inserting diluted feces from someone with a healthy intestinal ecosystem can restore microbial peace. The healthy microbes in the transplant soon crowd out the C. difficile.
The most recent study, done in the Netherlands and published earlier this year in the New England Journal of Medicine, found fecal transplants cured 15 of 16 people with recurring C. difficile infections. That’s a 93-percent success rate, compared to less than 30 per cent for standard antibiotic therapy.
When Edelmann went into the hospital in September 2011, she had no idea a fecal transplant was in her future. She also had no idea where she had picked up the C. difficile, but the microbe is commonly found in public washrooms, on pets and even on food.
Antibiotics prescribed to her after a tooth extraction appear to have triggered her infection. The drugs can kill off friendly bacteria in the gut that normally keep C. difficile at bay. With them gone, C. difficile is free to proliferate.
Edelmann spent three days in hospital with an intravenous drip to rehydrate her body. She was given vancomycin, a potent antibiotic that can knock back virulent C. difficile. Edelmann then headed home with a 10-day supply of the drug. The “vanco” worked its magic and life went back to normal.
But within a month, the C. difficile and the diarrhea returned.
Edelmann was prescribed more vancomycin, a routine that continued for the next year. The drug would knock the C. difficile back, but every time she finished taking it, the diarrhea recurred. The 62-year-old mother of two adult children had become what infectious-disease specialists call a “multiple relapser.” Like thousands of other Canadians, she could not shake C. diff.
Doctors told Edelmann she’d likely have to take vancomycin for life — a daunting prospect considering the drug cost her $2,130 for 120 capsules, about a six-week supply. “It’s very, very expensive,” Edelmann said in a recent interview in her home.
The bill could be well over $350,000 if she had to take the drug for the next 20 years.
Then a friend mentioned how Eu- ropean doctors were treating recurrent C. difficile with fecal transplants in which diluted fecal matter is sent down a nose tube. Edelmann didn’t like the sound of that. But the prospect of taking vancomycin for life wasn’t appealing either. Provincial drug plans tend to provide only limited coverage for it.
So she went to see Dr. Mark Miller, former head of infectious diseases at Montreal’s Jewish General Hospital. He is one of several doctors doing fecal transplants — also known as human biotherapy, bacteriotherapy and human-probiotic infusion — on an experimental basis.
The idea is not new. Chinese doctors prescribed the drinking of liquefied feces as a treatment for severe diarrhea and food poisoning in the fourth century. Veterinarians treat sick cows and horses with transplants of microbe-laden feces and rumen from healthy animals. In 1958, doctors in Colorado reported fecal transplants could “re-establish the balance of nature” in patients with recurrent diarrhea.
There was never much demand for the transplants, however, until virulent new strains of C. difficile emerged in 2000. In the U.S., C. difficile now causes 250,000 infections and kills 14,000 people each year.
Canadian statistics are hard to come by, but a recent study estimates C. difficile causes 37,900 infections a year at a cost of $272 million to the health care system. Hundreds of Canadians a year die after becoming infected with C. difficile, most often elderly individuals who pick up the microbe in hospitals and nursing homes. And many more end up like Edelmann, with stubborn infections they can’t get rid of.
“You are pretty much guaranteed to have relapse after relapse if you ever stop treatment,” Miller says of people with recurrent C. difficile. “That’s where the fecal transplants come in.”
The transplants are far from mainstream. Toronto infectious disease specialist Dr. Susy Hota says more research is needed to prove they are effective and safe. Others feel it could be just a matter of time before transplanting fecal material — of perhaps a refined mixture of key intestinal microbes — becomes routine.
Doctors are experimenting with different ways of transplants feces. The Europeans have gone the nasal route — “very unpleasant if you burp,” says Miller. Some doctors spray the fecal transplant into the colon with a colonoscope, a procedure for which they can bill provincial health plans.
Miller, following the lead of Dr. Thomas Louie, an infectious disease specialist at Calgary’s Peter Lougheed Hospital, opted for a low-tech, minimally invasive approach.
It’s basically an enema that involves infusing patients with liquefied diluted feces from donors. The donor is preferably someone the recipient lives with, as people who live together tend to have similar microbial ecosystems.
Patients go off their vancomycin a day or two before the transplant to clear it from their bodies. Donors are screened to ensure they won’t pass on parasites, HIV or other infectious organisms. On the day of the transplant, the donor provides a fecal sample. It is blended with saline solution; Miller buys blenders in bulk at Walmart and tosses them after a single use.
The fecal mixture is poured through a steel wool filter, then into an enema bag. The liquid is then infused into the intestine using a rectal tube. The patient lies on one side for about 20 minutes before changing positions to encourage the fluid to migrate up the colon to where C. difficile resides. Total cost of Miller’s set up: about $120. The blender and enema bag ring in at $40, plus another $80 for the tests that screen the donor for pathogens.
Researchers suspect the bacteria in the transplanted feces crowd out the C. difficile and restore a healthy microbial balance in the recipient’s colon. Miller says C. difficile can still persist in low levels in the recipient’s gut but stops causing diarrhea. “It’s pretty amazing,” he says.
Edelmann arrived at the hospital in September 2012 with a fecal sample from a close friend. An hour later, it was infused into her intestines. “There was no pain, no problem,” says Edelmann. “It was nothing.”
Within days, she knew it had worked. A year later, she has not relapsed. “I’m free.” she says with a big smile.