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  • Clostridium difficile : A controversial treatment with 90-95% success rate claimed

    Source: http://www.thespec.com/News/Local/article/437070

    Out of Control: Part V: Messy, disgusting and a lifeline
    Even some doctors recoil at the mention of fecal transplants. But the few healers in Canada who offer them are claiming a 90 to 95 per cent success rate.


    September 18, 2008
    Carmela Fragomeni
    The Hamilton Spectator

    A controversial therapy considered messy and disgusting is gaining attention as a possible cure for severe C. difficile.

    Fecal transplants involve taking stool from a healthy person, usually a relative, and injecting it into someone else's bowels.

    The goal is to counter C. diff in the infected person's intestines by adding a mix of good bacteria from a healthy person's stool.

    Although it makes many people squeamish, the therapy has cured C. diff in limited documented cases in Scandinavia, the United States and Australia.

    A 2004 Journal of Clinical Gastroenterology review of 36 reported cases found 33 patients, or almost 92 per cent, were cured. Some physicians who perform the treatment put their success rate even higher.

    Proponents of fecal transplants hope a proposed clinical trial in Toronto will give the therapy a level of credibility it hasn't reached yet. The proposal is under review by the University Health Network's ethics committee and by Health Canada.

    The study would compare standard treatment for C. diff with fecal transplants in about 150 patients.

    C. diff expert Dr. John Bartlett of Johns Hopkins University in Baltimore believes fecal transplants are the best C. difficile treatment, except "the aesthetics stink." It's the only way to replace all of the 400 microbial species of flora in the colon, he says.


    C. difficile is an often debilitating, painful bacterial infection that attacks the gastrointestinal tract, causing relentless diarrhea, fever, dehydration and sometimes death.

    A Spectator tally shows at least 460 patients infected with C. diff have died at 22 Ontario hospitals since 2006 -- including 91 at Joseph Brant Memorial Hospital in Burlington.

    One of them was Margery Strutt. Her son, Howard Strutt of Burlington, says he tried to get a fecal transplant for his 81-year-old mother, who suffered through five bouts of C. diff before dying Sept. 15, 2007, at Jo Brant.

    But he could not find a willing doctor.

    He says one Jo Brant specialist told him, "That's disgusting."

    Only a small number of physicians in the world do the transplants, including three in Canada.

    They claim a 90 to 95 per cent success rate and blame a reluctance by others to use the therapy on the "ick factor."

    Fecal transplants are administered through an enema or by a tube down the throat to the intestines.


    The treatment is one of many new approaches to combat vicious new strains of the common hospital disease.

    Maggots -- first choice for wound care in the Middle Ages -- are today being culled for secretions to use in new drugs against superbugs, scientists at Swansea University in Wales reported this summer.

    And probiotics -- naturally occurring micro-organisms that encourage good bacteria to grow in the digestive system -- are now in common use as a way of restoring intestinal balance to ward off C. diff.

    There's new public interest in fecal transplants these days, as C. diff death and infection rates rise.

    But doctors opposed to fecal transplants say the therapy is unproven because there are no clinical studies comparing a controlled group getting transplants with another group that is not.

    "If you really want to prove this is better than standard treatment, you really need to ... compare the two treatments (transplants and standard drugs), and that's never been done," says Dr. Michael Libman, a Montreal infectious disease expert.


    Replacing all the bacteria in the colon, which transplants are meant to do, is also "technically quite a chore," he says.

    Australia's Dr. Thomas Borody rejects the need for studies, saying "virtually everybody" treated has been cured.

    He has done fecal transplants for 22 years at his Sydney clinic.

    One Toronto woman who had the treatment in 2005 credits it with saving her life after a long fight with C. difficile.


    Marcia Munro, 48, believes she wouldn't be alive and healthy today if her doctor hadn't referred her to Calgary expert Dr. Tom Louie for a transplant.

    Her sister Wendy Sinukoff, who donated the healthy stool, says Munro's recovery was like a miracle.

    "Within 24 hours, she was better."

    Fecal transplant costs are not covered in Alberta, so Louie has done them mostly for free for 12 years.

    "If your bowels are misbehaving (like that) ... you would be terrorized," he says.

    The first of Louie's 48 transplants was in 1996, when he had a patient who searched everywhere, including the famed Mayo Clinic, for help.

    He says his success rate is 95 per cent.


    Dr. Mike Silverman, an infectious disease specialist from Ajax, says his first transplant patient was an elderly patient whose C. diff relapses put her in intensive care four years ago.

    "It worked magic," he says. "She didn't have any more diarrhea."

    Silverman has performed nine transplants so far, all successful, he says.

    He screens donors and prepares patients at his office. But he instructs patients how to mix the stool in a solution at home in a blender and give themselves the enema.

    He won't do the transplants in his office for practical purposes -- he would have to stop seeing his other patients in that room so it could be properly sanitized.

    Dr. Diane Langelier of Sherbrooke, Que., performs the therapy in hospital -- doing 31 transplants over 15 years.

    Langelier stumbled onto the procedure. While researching how to help a patient who struggled through six relapses of C. diff, she found a journal article describing how to prepare and administer a fecal transplant.

    "It's a very good treatment and very easy to make," she says.

    Langelier administered the transplants by enema until the hypervirulent superbug strain appeared in Quebec, killing at least 2,000 since 2002. Now she uses two methods together -- a colonoscopy enema and a tube down the throat to the colon -- to ensure "100 per cent success."


    At Quinte Health Care, infection control chief Dr. Michael de la Roche recalls one occasion when a fecal transplant has been used there.

    But he says he is waiting for more evidence that it works before they consider performing more.

    "It's not for the faint of heart," he says.

    Instead, all patients on antibiotics at Quinte, which has four sites in eastern Ontario, get a daily probiotic tablet five times stronger than yogurt to prevent C. diff.

    While fecal transplants are still rare in Canada, they've become more acceptable in some European countries.

    In the Netherlands, the transplants are considered "a quite logical way to restore intestinal flora," according to Dr. Els van Nood of Amsterdam.

    A clinical trial of 120 C. diff patients is currently under way there.


    "If this succeeds, and we prove that fecal transplants are so much more successful than antibiotics for the treatment of recurrent disease, doctors and patients will be more easily convinced of the relative simplicity and success of this treatment," van Nood said in an e-mail.

    Hospital fecal transplants are common in Norway, according to Dr. Arnold Berstad. He does 10 to 15 a year there because "often, it is a question of life or death."

    Transplant expert Dr. Johan Bakken of Duluth, Minn., says the therapy may be a good first-line treatment on patients with the virulent superbug strain "because these people get so sick, so fast that there's a much higher mortality rate."

    Ajax's Silverman says fecal transplants won't stop an outbreak like Jo Brant's.


    Howard Strutt will never know if a fecal transplant would have saved his mother's life after her repeated battles with C. diff at the Burlington hospital.

    But he believes it was certainly worth a try.

    Out Of Control is a three-month investigation by Spectator reporters Carmela Fragomeni, Naomi Powell and Joan Walters into killer superbug C. difficile. It examines the crisis in patient safety in hospitals, the response by government and hospital administrators and the impact on victims and families. In May, Joseph Brant Memorial Hospital revealed 91 patients infected with C.diff died from May 2006 to December 2007 in the worst recorded outbreak in Ontario history. Hundreds of patients with C. diff have died in Ontario hospitals since 2006. JOAN WALTERS can be reached at 905-526-3302 or jwalters@thespec.com. NAOMI POWELL can be reached at 905-526-4620 or npowell@thespec.com. CARMELA FRAGOMENI can be reached at 905-526-3392 or cfragomeni@thespec.com

  • #2
    Re: Clostridium difficile : A controversial treatment with 90-95% success rate claimed

    Source: http://www.nature.com/nature/journal...ture13828.html



    Nature | Letter
    Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile

    Charlie G. Buffie,
    Vanni Bucci,
    Richard R. Stein,
    Peter T. McKenney,
    Lilan Ling,
    Asia Gobourne,
    Daniel No,
    Hui Liu,
    Melissa Kinnebrew,
    Agnes Viale,
    Eric Littmann,
    Marcel R. M. van den Brink,
    Robert R. Jenq,
    Ying Taur,
    Chris Sander,
    Justin Cross,
    Nora C. Toussaint,
    Joao B. Xavier
    & Eric G. Pamer

    Affiliations
    Contributions
    Corresponding author

    Nature
    (2014)
    doi:10.1038/nature13828

    Received
    04 May 2014
    Accepted
    03 September 2014
    Published online
    22 October 2014

    The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens1. Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens2. Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients3. Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion...

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