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C difficile: Synthetic Stool Substitute Clears Infection
A few months ago I posted a medical article about fecal transplantation as a very successful approach to treating/curing C Difficile. I believe I posted it here it but it may have been on another forum. Anyway, it seems as though an alternative and much less objectionable approach has been found/created.
C difficile: Synthetic Stool Substitute Clears Infection
Jenni Laidman
Jan 10, 2013
A synthetic stool substitute successfully ended bouts of recurrent antibiotic-resistant Clostridium difficile in a proof-of-principle study published January 9 in the inaugural issue of Microbiome.
The study, which involved just 2 patients, suggests the promise of an off-the-shelf alternative to the transplantation of donor stool to control antibiotic-resistant intestinal bacteria.
Elaine O. Petrof, MD, assistant professor, Department of Medicine, Infectious Diseases, Kingston General Hospital, Queen's University, Ontario, Canada, and colleagues created the human synthetic stool mixture by culturing the stool microbial diversity of a healthy 41-year-old woman and brewing a mixture of 33 different intestinal bacteria isolated in pure culture. They named the synthetic stool mixture RePOOPulate.
The bacterial mixture was infused into the colon of 2 patients in their 70s, both of whom were infected with a hypervirulent strain of C difficile, ribotype 078, and who had failed at least 3 courses of antibiotic therapy.
Both patients returned to normal bowel patterns in 2 or 3 days and remained symptom-free for 6 months. At that time, rRNA sequences representing the RePOOPulate mixture made up 25% of the gut bacterial population.
"It's an interesting paper and pretty exciting," Colleen Kelly, MD, a gastroenterologist from the Center for Women's Gastrointestinal Medicine at the Women's Medicine Collaborative, Providence, Rhode Island, told Medscape Medical News in an email. Dr. Kelly was not involved in the current study.
"I've been doing fecal transplants for nearly 5 years and have treated 90 patients with about a 94% success rate. Identifying a suitable donor can be difficult in some patients. Also, the cost of donor screen labs (which is not always covered by insurance) is expensive. The process of donor eligibility determination is time consuming, and some doctors face institutional barriers that prevent them from offering [fecal microbiota transplantation]. If a safe, effective product was available, many more patients could be treated with [fecal microbiota transplantation]. Additionally, this compound would make the necessary clinical trials much easier to do." Dr. Kelly is involved in what is considered the first randomized trial of fecal transplant for recurring C difficile.
C difficile, a Gram-positive, anaerobic bacillus that produces a toxin, is the source of 15% to 25% of antibiotic-associated diarrhea.
Researchers in the Canadian study cultured 62 different bacterial isolates from donor stool, identifying them by 16S rRNA gene sequencing and profiling them for antibiotic susceptibility. Any isolate resistant to antibiotics was eliminated. The result was 33 isolates sensitive to a range of antibiotics and relatively easy to culture under anaerobic conditions. The researchers used the profile of a healthy donor as a guide to relative abundances of species to include in the probiotic mixture. The purified intestinal bacterial cultures were grown in "Robo-gut" equipment that mimics the environment within the large intestine.
The authors note that the creation of a synthetic mixture allows for control of the composition of the bacteria the patient will receive in a reproducible species mix. It also eliminates the worry of viruses or other pathogens that can ride along in donor stool.
In the past, researchers have tried single probiotics in attempts to clear C difficile infection. "They have not really ever [been] shown to manage multiply recurrent C diff," said Cliff McDonald, MD, chief, Prevention and Response Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia. "I think it's conceivable [to use] a cocktail or several cocktails — there might be quite a few that work pretty well. It might be hard to say which cocktail works better than the other. It may depend upon the people treated, too," Dr. McDonald told Medscape Medical News. He was not involved in the Microbiome study.
Dr. McDonald also noted that a group from the Sanger Institute published a paper in October 2012 in PLoS Pathogens reporting the successful use of a cocktail of 6 bacteria to clear C difficile infection in mice.
The results of the Canadian study are "fantastic," said Mayur Ramesh, MD, senior staff physician in infectious disease, Henry Ford Hospital, Detroit, Michigan. "That's what everybody's looking for, including our own team." Dr. Ramesh has developed a simplified method of preparing donor stool for transplant and treatment of C difficile infection, but was not involved in the current study.
A synthetic substance could resolve the significant "yuck" factor that makes physicians unwilling to perform stool transplants, according to Dr. Ramesh. "Nobody wants to do it," he said.
Patients, in contrast, accept the treatment easily. "I have not a single patient refuse. I have people fly in from California, and I'm in Detroit," he said. "American doctors are shunning things like this, even though it saves lives. This is the best treatment for C difficile."
The newly published study included a 74-year-old white woman who suffered 6 episodes of recurrent C difficile infection during 18 months after orthopedic surgery and preoperative treatment with cefazolin, and a 70-year-old white woman who had 3 episodes of recurrent C difficile infection after treatment with cefazolin for cellulitis. Both women received additional antibiotics after the probiotic transfer. One patient received several courses for recurrent urinary tract infection and the second for recurrent cellulitis. Still, by the end of 6 months they had no return of C difficile infection symptoms and maintained a diverse population of gut bacteria.
Recurrent C difficile infection is largely a result of the inability of normal intestinal flora to recover from antibiotic treatment.
http://www.medscape.com/viewarticle/777515?src=wnl_edit_medn_wir&spon=34
C difficile: Synthetic Stool Substitute Clears Infection
Jenni Laidman
Jan 10, 2013
A synthetic stool substitute successfully ended bouts of recurrent antibiotic-resistant Clostridium difficile in a proof-of-principle study published January 9 in the inaugural issue of Microbiome.
The study, which involved just 2 patients, suggests the promise of an off-the-shelf alternative to the transplantation of donor stool to control antibiotic-resistant intestinal bacteria.
Elaine O. Petrof, MD, assistant professor, Department of Medicine, Infectious Diseases, Kingston General Hospital, Queen's University, Ontario, Canada, and colleagues created the human synthetic stool mixture by culturing the stool microbial diversity of a healthy 41-year-old woman and brewing a mixture of 33 different intestinal bacteria isolated in pure culture. They named the synthetic stool mixture RePOOPulate.
The bacterial mixture was infused into the colon of 2 patients in their 70s, both of whom were infected with a hypervirulent strain of C difficile, ribotype 078, and who had failed at least 3 courses of antibiotic therapy.
Both patients returned to normal bowel patterns in 2 or 3 days and remained symptom-free for 6 months. At that time, rRNA sequences representing the RePOOPulate mixture made up 25% of the gut bacterial population.
"It's an interesting paper and pretty exciting," Colleen Kelly, MD, a gastroenterologist from the Center for Women's Gastrointestinal Medicine at the Women's Medicine Collaborative, Providence, Rhode Island, told Medscape Medical News in an email. Dr. Kelly was not involved in the current study.
"I've been doing fecal transplants for nearly 5 years and have treated 90 patients with about a 94% success rate. Identifying a suitable donor can be difficult in some patients. Also, the cost of donor screen labs (which is not always covered by insurance) is expensive. The process of donor eligibility determination is time consuming, and some doctors face institutional barriers that prevent them from offering [fecal microbiota transplantation]. If a safe, effective product was available, many more patients could be treated with [fecal microbiota transplantation]. Additionally, this compound would make the necessary clinical trials much easier to do." Dr. Kelly is involved in what is considered the first randomized trial of fecal transplant for recurring C difficile.
C difficile, a Gram-positive, anaerobic bacillus that produces a toxin, is the source of 15% to 25% of antibiotic-associated diarrhea.
Researchers in the Canadian study cultured 62 different bacterial isolates from donor stool, identifying them by 16S rRNA gene sequencing and profiling them for antibiotic susceptibility. Any isolate resistant to antibiotics was eliminated. The result was 33 isolates sensitive to a range of antibiotics and relatively easy to culture under anaerobic conditions. The researchers used the profile of a healthy donor as a guide to relative abundances of species to include in the probiotic mixture. The purified intestinal bacterial cultures were grown in "Robo-gut" equipment that mimics the environment within the large intestine.
The authors note that the creation of a synthetic mixture allows for control of the composition of the bacteria the patient will receive in a reproducible species mix. It also eliminates the worry of viruses or other pathogens that can ride along in donor stool.
In the past, researchers have tried single probiotics in attempts to clear C difficile infection. "They have not really ever [been] shown to manage multiply recurrent C diff," said Cliff McDonald, MD, chief, Prevention and Response Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia. "I think it's conceivable [to use] a cocktail or several cocktails — there might be quite a few that work pretty well. It might be hard to say which cocktail works better than the other. It may depend upon the people treated, too," Dr. McDonald told Medscape Medical News. He was not involved in the Microbiome study.
Dr. McDonald also noted that a group from the Sanger Institute published a paper in October 2012 in PLoS Pathogens reporting the successful use of a cocktail of 6 bacteria to clear C difficile infection in mice.
The results of the Canadian study are "fantastic," said Mayur Ramesh, MD, senior staff physician in infectious disease, Henry Ford Hospital, Detroit, Michigan. "That's what everybody's looking for, including our own team." Dr. Ramesh has developed a simplified method of preparing donor stool for transplant and treatment of C difficile infection, but was not involved in the current study.
A synthetic substance could resolve the significant "yuck" factor that makes physicians unwilling to perform stool transplants, according to Dr. Ramesh. "Nobody wants to do it," he said.
Patients, in contrast, accept the treatment easily. "I have not a single patient refuse. I have people fly in from California, and I'm in Detroit," he said. "American doctors are shunning things like this, even though it saves lives. This is the best treatment for C difficile."
The newly published study included a 74-year-old white woman who suffered 6 episodes of recurrent C difficile infection during 18 months after orthopedic surgery and preoperative treatment with cefazolin, and a 70-year-old white woman who had 3 episodes of recurrent C difficile infection after treatment with cefazolin for cellulitis. Both women received additional antibiotics after the probiotic transfer. One patient received several courses for recurrent urinary tract infection and the second for recurrent cellulitis. Still, by the end of 6 months they had no return of C difficile infection symptoms and maintained a diverse population of gut bacteria.
Recurrent C difficile infection is largely a result of the inability of normal intestinal flora to recover from antibiotic treatment.
http://www.medscape.com/viewarticle/777515?src=wnl_edit_medn_wir&spon=34
Great story. Thanks for sharing it.
Mike
Mike
I was very lucky to have a patient MANY years ago who was given one of the first fecal transplants. She was in a hospital I worked at, and c-diff had ravaged her, she was down to 80-some pounds, it was awful. They tried, unsuccessfully to treat it, manage it for a year. Without doing something, she would have surely died. She had a feeding tube, was receiving TPN, could barely walk. She was the sweetest woman, in her early 50's and how we would joke with her about her poop donor (a sister), and all kinds of other things related to the procedure. She was so special to us..we had had her as a patient for LONG periods of time over the course of a year...we had all grown very close to her.
Her doctors here found a doc willing to do it, via c-scope at Cleveland Clinic. She came back to visit us about 6 months later, OMG, she had gained almost all of her weight back, looked fantastic. It worked, and she was SO happy!! It was very experimental back then (probably around 2002), now many docs will do a fecal transplant in cases of treatment resistant c-diff..
I think this is awesome! It will be much easier to convince people to try this. I love these kinds of stories!!
Her doctors here found a doc willing to do it, via c-scope at Cleveland Clinic. She came back to visit us about 6 months later, OMG, she had gained almost all of her weight back, looked fantastic. It worked, and she was SO happy!! It was very experimental back then (probably around 2002), now many docs will do a fecal transplant in cases of treatment resistant c-diff..
I think this is awesome! It will be much easier to convince people to try this. I love these kinds of stories!!
I live with IBS too. It can really be a miserable thing to live with.
My husband has IBS. Anything that might give him some relief is worth considering.
I do like the name!
I do like the name!
"RePOOPulate. That is an awesome name, lol. :-) "
Yes it is..lol
"It stuck me as telling that the patients and doctors were so far apart."
That IS strange how the Dr's and patients are so far apart on this..
Yes it is..lol
"It stuck me as telling that the patients and doctors were so far apart."
That IS strange how the Dr's and patients are so far apart on this..
I got my numbers wrong on the percentages. Sorry about that.
From: Systematic Review: Faecal Microbiota Transplantation in the Management of Inflammatory Bowel Disease
"...Barriers to the adoption of FMT as a therapeutic tool include the absence of high-quality evidence for its efficacy, patient and clinician acceptance and potential safety concerns. It has been suggested that perhaps it is clinicians rather than patients who are resistant to the use of FMT as a viable treatment option.[49] In a survey of 73 physicians, 25 (34%) indicated they would be unwilling to perform the procedure with the most common concerns being patient acceptance and tolerability (71%) followed by safety (60%) and efficacy (57%).[50] In contrast, in a recent qualitative study exploring readiness for FMT in patients with UC, the majority of patients wished the procedure was already available and most viewed it as being safer than current available therapies, especially steroids or biological therapies.[51] In a quantitative extension of this study, the majority of UC patients were interested or willing to consider FMT despite reporting disease control with IBD medications.[52] The most important concerns were around donor selection and screening as a means of eliminating the potential risk of transmission of infectious agents. This risk can be reduced with the implementation of thorough screening protocols. Interestingly, this systematic review highlights that close relatives are frequently selected as stool donors. However, recent evidence indicates that the relatives of patients with IBD themselves have altered microbiota,[53] and that this dysbiosis may itself be partly responsible for their elevated risk of IBD.[54] Investigation of the ideal stool donor in FMT in the context of IBD is warranted.
http://www.medscape.com/viewarticle/770009_4
From: Systematic Review: Faecal Microbiota Transplantation in the Management of Inflammatory Bowel Disease
"...Barriers to the adoption of FMT as a therapeutic tool include the absence of high-quality evidence for its efficacy, patient and clinician acceptance and potential safety concerns. It has been suggested that perhaps it is clinicians rather than patients who are resistant to the use of FMT as a viable treatment option.[49] In a survey of 73 physicians, 25 (34%) indicated they would be unwilling to perform the procedure with the most common concerns being patient acceptance and tolerability (71%) followed by safety (60%) and efficacy (57%).[50] In contrast, in a recent qualitative study exploring readiness for FMT in patients with UC, the majority of patients wished the procedure was already available and most viewed it as being safer than current available therapies, especially steroids or biological therapies.[51] In a quantitative extension of this study, the majority of UC patients were interested or willing to consider FMT despite reporting disease control with IBD medications.[52] The most important concerns were around donor selection and screening as a means of eliminating the potential risk of transmission of infectious agents. This risk can be reduced with the implementation of thorough screening protocols. Interestingly, this systematic review highlights that close relatives are frequently selected as stool donors. However, recent evidence indicates that the relatives of patients with IBD themselves have altered microbiota,[53] and that this dysbiosis may itself be partly responsible for their elevated risk of IBD.[54] Investigation of the ideal stool donor in FMT in the context of IBD is warranted.
http://www.medscape.com/viewarticle/770009_4
BTW, I agree about the name. It's a bit strange but extremely descriptive.
When they polled patients and doctors about fecal transplantation 70% of doctors said they would be reluctant to offer the therapy because the patients would not embrace it. Roughly 80% of the chronic C Difficile patients said they'd agree to the procedure. This disease can be a prolonged one which lasts 1 year and longer and is extremely unpleasant. It stuck me as telling that the patients and doctors were so far apart.
RePOOPulate. That is an awesome name, lol. :-)
This is a really wonderful advancement. I honestly can't imagine having a fecal transplant--but then again, I can't imagine struggling with c-diff. I know if any situation is desperate enough to come down to life and death, people are usually willing to try anything to survive.
This is a really wonderful advancement. I honestly can't imagine having a fecal transplant--but then again, I can't imagine struggling with c-diff. I know if any situation is desperate enough to come down to life and death, people are usually willing to try anything to survive.
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