Fighting microbes with microbes: Can fecal transplants work where antibiotics fail?

Celine Edelmann, who had a fecal transplant last year, a treatment for her chronic C.diff infection, poses in her home in Montreal, July 16, 2013.
Celine Edelmann, who had a fecal transplant last year, a treatment for her chronic C.diff infection, poses in her home in Montreal (CHRISTINNE MUSCHI PHOTO FOR POSTMEDIA NEWS)

Published November 12, 2013

MONTREAL – Céline 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 back 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 quickly 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-per-cent 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 there would be a fecal transplant in her future.

She also has 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 to her Montreal flat 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 had 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, pulling out the receipts for her prescriptions.

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 European doctors were treating recurrent C. difficile with fecal transplants.

Diluted fecal matter was 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.

The bill could be well over $350,000.

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. And 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 United States, C. difficile now causes 250,000 infections and kills 14,000 people.

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 so it won’t kill the incoming bacteria from the fecal transplant. 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 Wal-Mart when they’re on sale and tosses them after a single use.

The fecal mixture is poured through a steel wool filter, then into an enema bag. The liquid, resembling dark chicken broth, 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.

No one can really explain why the transplants work, but 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 being infused into her intestines.

“There was no pain, no problem,” says Edelmann, in her calm, unflappable manner. “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.

Al Booth, in Hamilton, Ont., had an even more harrowing experience this spring. It, too, led to a fecal transplant.

Retired autoworker Al Booth.

Retired autoworker Al Booth.

The former autoworker and wrestling champion was raced to hospital by ambulance in June when virulent C. difficile took hold in his gut. His recurring problems with C. difficile had started in December 2011, shortly after he was given intravenous antibiotics for an eye infection.

In hospital with C, diff., “you just lay there like you’re in a trance,” says Booth, 85, recalling how nurses in protective gowns would appear to check his vitals and clean him up. “Your bowels let go,” he says. “Then they change the diaper, and about an hour later they change it again.”

He had such a raging fever and relentless diarrhea that doctors at one point asked his family whether Booth wished to be resuscitated if the decline continued.

Booth pulled through. He has also joined Canada’s largest fecal transplant trial in the hope of restoring a healthy microbial ecosystem in his intestines. He is one of 156 people who will receive either fresh or frozen feces in the trial sponsored by McMaster University.

Booth received his transplant in late July and saw positive results within days.

“I’d highly recommend it,” he says. “I wouldn’t put up with C. diff.” As for antibiotics. “I’ll be steering clear of them now,” he says.

Dr. Christine Lee, an infectious disease specialist at St. Joseph’s Healthcare in Hamilton, says there is not only a need for more effective treatment for C. difficile but for better education about the dangers of antibiotics.

“We need warnings on antibiotics,” says Lee. Doctors and dentists prescribing the medications should alert patients and their families to the dangers, she says, so people can seek treatment early and stop the “offending antibiotic” if symptoms of C. difficile develop.

– Research for this story was funded in part by a journalism award from the Canadian Institutes of Health Research.

A few fecal facts:

Canadian health administrators, who until recently shunned fecal transplants as unproven and risky, are permitting experimental treatment in several hospitals. And Health Canada, while not endorsing fecal transplants, is allowing “investigational” clinical trials:

– A “fresh-verses-frozen” fecal transplant trial involving 156 patients is underway at McMaster University in Hamilton and expanding to include patients in Vancouver, Edmonton and Kingston. Six donors, who have been screened for disease, lead healthy lifestyles and “are regular,” provide the feces. If frozen stool works as well as transplants with fresh feces, they could be stored in “poop” banks and used in hospitals that don’t have microbiology labs or have access to screened donors. “Logistically it would be so much easier to offer,” says Dr. Christine Lee at St. Joseph’s Healthcare in Hamilton, who heads the trial.

– “RePOOPulate,” created by Emma Allen-Vercoe, at the University of Guelph, aims to reduce fecal transplants to the essential microbial players capable of restoring healthy gut ecosystems. Allen-Vercoe and her colleague, Dr. Elaine Petrof at Queen’s University in Kingston, have tested their RePOOPulate mixture of 33 strains of fecal microbes on two elderly people, who were both quickly cured of their recurrent C. difficile.

– Pills packed with fecal microbes could make fecal transplants even more palatable. Dr. Thomas Louie’s group at the Peter Lougheed Hospital in Calgary is custom-making capsules packed with microbes harvested from fresh feces. Ninety minutes after the capsules are swallowed, they release their living cargo into the patient’s intestine. The microbes start to multiply and establish a healthy gut ecosystem. Louie reports the pills, swallowed by about 40 patients, work as well if not better than the fecal transplants he has administered be enema.

– Dr. Susy Hota, at Toronto’s University Health Network, is recruiting 140 people with recurrent C. difficile for a trial that aims to compare fecal transplants with standard drug treatment. She feels it is premature to start offering fecal transplants as routine therapy, and warns that symptoms of irritable bowel syndrome and colitis can be mistaken for C. difficile infections. “I think we need to wait for information, to be quite honest,” says Hota.  She also notes that “we have no standardization of our (fecal transplant) practices and we don’t know which is the optimal way of doing it.”


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