Crohn's Disease, Acne and Fecal Microbiota Transplant In Teenager - Remission Without Medication! 27 July 2013

I have hesitated in sharing my son's story with Crohn's Disease and the success we have had with FMT (fecal microbiota transplantation) until now because I didn't want to do so prematurely.

My son is 15 years old.  To protect his privacy, I will call him Jake, although that is not his real name :-).

Jake was diagnosed with Crohn's Disease a few days before his 13th birthday.  It was widespread ulceration, inflammation and infection throughout his duodenum, terminal ileum, ascending colon, descending colon and rectum.  It was a "gut-wrenching" time for me as a mother to an only child, especially after being told how very serious this disease is, how extensively he had it, that he would have it for the rest of his life, and probably do poorly in the long-term because he was so young at diagnosis. 

I was worried sick with the long term consequences of my son taking immune-suppressive drugs (in his case, Imuran) - on the other hand I was terrified of the consequences of Crohn's Disease and felt we were between a "rock and a hard place".  I cannot begin to put into words just how heartbroken and helpless I felt, but I am sure that any parent who reads this will understand.

Professor Tom Borody was recommended to us by a family friend as being an outstanding gastroenterologist.  Unfortunately he was unable to treat Jake until he turned 14 as he was a paediatric patient, however tests he was able to order showed that Jake also had a strain of c-diff (clostridium difficile) - it was not the worst strain, but Prof. Borody felt that we needed to get rid of that first.  It was what he called a "super infective".

Within days of his 14th birthday, Jake had a gastroscopy and colonoscopy.  The Imuran had certainly helped to take care of the crohn's in his colon - however his terminal ileum was still swollen, inflamed and pussey.  His duodenum, still had some crohn's-like ulcerations.  Prof. Borody recommended FMT to kill off the c-diff and we proceeded to have suitable family members tested as potential donors.  Jake began a three week course of oral vancomycin to weaken the c-diff and then in April 2012 had his first FMT via colonoscopy- his terminal ileum was still very inflamed and swollen.  I continued to administer FMT treatments to Jake at home and his 14 year old cousin was the donor.  We also continued his Imuran.

A remarkable and unexpected bonus to having the FMT was that acne that had plagued Jake for the past year and a half had completely disappeared 7 days after treatment began.  It has never returned!!

In November of 2012 Jake had a colonoscopy and endoscopy.  To Prof. Borody's surprise, Jake's colonoscopy was perfect - the terminal ileum looked normal, as if there had never been a problem!  The only trace was one single tiny erosion in his duodenum.  There was no trace of c-diff either!

As advised, we reduced his Imuran and gradually over the next few months.  Jake was completely off his medication by March 2013, so as at the time of writing, it's been almost five months.  Jake is growing tall, his appetite is huge (perfectly normal for a healthy teenage boy) and he is putting on weight appropriately for his age.  I still do top-up FMT treatments every 3 to 4 weeks - it's difficult to know exactly when the right time to stop is - in total he has had well over 115 treatments.  Prof. Borody says that Jake needs to develop his own microbiota.  

I do not know if FMT offers a cure for crohn's disease - but I do know that there is no way my son would have been able to sustain any remission without medication prior to this as we had tried a couple of times to reduce his Imuran but both times his symptoms came back within two weeks.  What I do know is that FMT has tremendous potential for Crohn's and other diseases and definitely needs further studies.  I also have to stress the importance of stringent donor testing.

I will keep you all posted in the months ahead of Jake's progress, but thus far, as a mother, I cannot be more delighted with how well this has gone.  I am also so incredibly thankful for Prof. Tom Borody for being one of those scientists who dares to think "outside the box".  It is because of doctors like him that medicine advances instead of remaining stagnant.  It is because of him that Jake's future is looking good instead of bleak and that I can cry tears of happiness and gratitude instead of despair.


(Please click here to read part 2 of "Jake's" Story - November 2013 (One year later) - Colonoscopy/Gastroscopy showing no sign of Crohn's Disease whatsoever - NOT even in his duodenum!)

Youngest Fecal Transplant Recipient "The Doctor's Exclusive Medical Miracales"

 

 

 

This is a video which aired on TV - great news for pediatric (child) patients with c-diff

 

 

Fecal Microbiota Transplantation - New England Journal of Medicine Reports 94% Cure Rate for C-difficile

The results of a randomized controlled study has been published in the New England Journal of Medicine this week which showed a 94% cure rate for clostridium difficile as opposed to 31% of patients taking the antibiotic vancomycin. The study was stopped prematurely becase the results were so outstanding for those who were given fecal transplant that it was considered to be unethical not to offer the treatment to all patients participating in the study. Read more below courtesy of the New England Journal.nbsp;  Here is a link to the study:

Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile — NEJM

and a link to the editorial written by Ciarán P. Kelly, M.D.

Fecal Microbiota Transplantation — An Old Therapy Comes of Age — NEJM

"Fecal Microbiota Transplantation — An Old Therapy Comes of Age

Ciarán P. Kelly, M.D.

January 16, 2013DOI: 10.1056/NEJMe1214816

In 1958, doctors in Denver administered feces by enema to their patients with fulminant, life-threatening pseudomembranous enterocolitis.1 The goal of this infusion of donor feces (also termed fecal microbiota transplantation [FMT]) was to “re-establish the balance of nature” within the intestinal flora to correct the disruption caused by antibiotic treatment. They reported “immediate and dramatic” responses and concluded that “this simple yet rational therapeutic method should be given more extensive clinical evaluation.” During the ensuing 50 years, the association between Clostridium difficile infection and pseudomembranous enterocolitis was established, and effective antimicrobial treatments were identified. Despite these advances, C. difficile became the most commonly identified cause of nosocomial infectious diarrhea in the United States. During the past decade, there has been an alarming increase in the incidence and severity of this disorder, with associated increases in mortality and economic cost.2

Although most patients with C. difficile infection have a response to antimicrobial therapy, approximately 25% have a recurrence after the initial treatment course.2 Patients with a first recurrence of C. difficile infection are more likely to have a second recurrence (risk, 35 to 45%), and for patients with multiple recurrences, the subsequent recurrence rates surpass 50%.2-4

Only patients with the most recalcitrant cases of C. difficile infection are likely to undergo FMT, usually out of desperation after multiple treatment approaches have failed.5,6 Yet, systematic review reveals that the reported efficacy of FMT in treating recurrent C. difficile infection is greater than 90%.6 So why has FMT not become routine therapy for C. difficile infection during the past 50 years? There are three main reasons: it is aesthetically unappealing, it is logistically challenging (in terms of harvesting and processing suitable donor material), and there is a lack of efficacy data from randomized, controlled trials.
 

The last impediment is addressed in a report on a randomized, controlled trial by van Nood et al.,7 now in the Journal. In this study, investigators compared the duodenal infusion of donor feces after vancomycin therapy and bowel lavage with vancomycin therapy either alone or with bowel lavage. The study was unblinded and imperfect. Nonetheless, the outcome favors FMT (81% response) above vancomycin therapy either alone (31%, P<0.001) or with bowel lavage (23%, P<0.001) in patients with relapsed C. difficile infection in whom standard therapy with vancomycin has failed. The trial was closed to new enrollment by its data and safety monitoring board after only 43 of a planned 120 patients had undergone randomization because almost all patients in the two control groups had a recurrence. The finding that FMT was effective in 81% of patients with recurrent C. difficile infection is consistent with a systematic review of uncontrolled case series in which FMT through the stomach or small intestine showed an overall response rate of 80%; the anecdotally reported overall response rate for FMT through colonoscopy or enema is 92%.6 Thus, this study and the previous case series yield consistent, strongly positive results.

The study by van Nood et al. is an important confirmation of the efficacy of FMT for recurrent C. difficile infection. Their findings will provide added stimulus to the ongoing efforts to address the other main impediments to the routine and widespread use of FMT. Natural antipathy toward fecal therapy can be reduced by banking suitable material from anonymous, screened donors.8 Such a system would both distance the recipient from the stool donation and provide physicians with readily accessible, quality-controlled treatment materials. Ultimately, the use of feces may be eliminated in favor of defined mixtures of cultured bacteria that confer colonization resistance against C. difficile, an approach that was pioneered by Tvede and Rask-Madsen in 1989 and is now being examined afresh.9 The later approach can also assuage concern regarding the inadvertent transmission of disease-causing pathogens through FMT. These advances can make intestinal microbiota therapy acceptable and accessible to most patients and their physicians. It will also facilitate the “more extensive clinical evaluation” of FMT for severe, refractory C. difficile infection, as first advocated in 1958.1

 

 

The significance of the study by van Nood et al. goes far beyond the treatment of recurrent or severe C. difficile infection. The burgeoning field of microbiome research, initially made possible by technologies to identify bacterial 16S ribosomal RNA in complex biologic samples, has alerted us to the abundant, diverse, and influential nature of the gut microbiota.10 Microbiome research has been expanded and complemented by methods to characterize the protein composition (proteomics) and metabolic processes (metabolomics) of the intestinal contents and those from other body sites. The results of this study represent a clear precedent in which planned therapeutic manipulation of the human intestinal microbiota can lead to demonstrable, clinically important benefits, thereby bringing FMT to the mainstream of modern, evidence-based medical practice.1,5-9 The study by van Nood et al. will encourage and facilitate the design of similar trials of intestinal microbiota therapy for other indications, such as inflammatory bowel disease, irritable bowel syndrome, prevention of colorectal carcinoma, and metabolic disorders, to name just a few.10 As such, it heralds the delayed adolescence of a broad and exciting new branch of human therapeutics.

References

1. 1
   Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958;44:854-859
   Web of Science
2. 2
   Kelly CP, LaMont JT. Clostridium difficile -- more difficult than ever. N Engl J Med 2008;359:1932-1940
   Full Text | Medline
3. 3
   Gerding DN, Johnson S. Management of Clostridium difficile infection: thinking inside and outside the box. Clin Infect Dis 2010;51:1306-1313
   CrossRef | Web of Science
4. 4
   McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994;271:1913-1918[Erratum, JAMA 1994;272:518.]
   CrossRef | Web of Science | Medline
5. 5
   Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol 2011;9:1044-1049
   CrossRef | Web of Science
6. 6
   Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 2011;53:994-1002
   CrossRef | Web of Science
7. 7
   van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013. DOI: 10.1056/NEJMoa1205037.
8. 8
   Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 2012;107:761-767
   CrossRef | Web of Science
9. 9
   Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989;1:1156-1160
   CrossRef | Web of Science | Medline
10. 10
    Shanahan F. The gut microbiota in 2011: translating the microbiota to medicine. Nat Rev Gastroenterol Hepatol 2011;9:72-74
    CrossRef | Web of Science

Clinics and Doctors Who Perform Fecal Microbiota Transplantation

We are compiling a list of doctors and hospitals around the world who have performed fecal microbiota transplants - the list will grow as more doctors start to use this procedure on their ailing patients.

We would love your help in compiling this list, so a comment with a name of a doctor/physician/medical professional and any information you can give would be very much appreciated!

Please don't try this procedure without qualified medical guidance and advice. It is essential that fecal doners be screened for various diseases including some which are contageous. This is why a list of doctors who are familiar with the procedure is important, so that those of you who feel fecal microbiota transplantation could be beneficial to you can seek out appropriate medical advice.

Doctors from around the world are listed below:

Australia

Professor Thomas Borody,

Centre For Digestive Diseases

Five Dock, Sydney

USA

Dr Lawrence J Brandt

Montefiore Medical Center
111 East 210th Street
Rosenthal Pavilion
Bronx, NY 10467

 

Wilfred Lee, MD

Gastroenterology

Internal Medicine

St Francis Medical Centre

2907 Keystone
Cape Girardeau, MO 63701

Dr. Alexander Khoruts

Gastroenterology (GI) Clinic

Phillips-Wangensteen Building
Clinic 1E
516 Delaware St. SE
Minneapolis, MN 55455

Sudhir K. Dutta, M.D.

Division Head of Gastroenterology,
Sinai Hospital of Baltimore
2411 W. Belvedere Avenue, Suite 305
Baltimore, MD 21215
Phone: 410-601-5392

 

Dr David Shepard

Tampa Endoscopy Center

4809 North Armenia Avenue

Suite 100

Tampa, Florida, 33603-1436

Phone:  (813) 658-5037

 

Canada

Dr Michael Silverman

Lakeridge Health
1 Hospital Court
Oshowa
Ontario, Canada
905-721-4717

UK 

Taymount Clinic
Clinic Director is Glenn Taylor
1/F, 16a High Street
Hitchin, Hertfordshire
SG6 1AT United Kingdom
Email Contact: enquiries@taymount.com
Website: http://www.taymount.com
Telephone: 0044 1462 712500

 

If you are trying to find a doctor who has had past experience in performing fecal microbiota transplants please comment in the box stating the area you live and how far you would be willing to travel for treatment and we will endeavour to locate an appropriate medical professional for you.

Stool Banks for Stool Doners?

According to an article in the Sydney Morning Herald, stool transplants (fecal microbiota transplantation) are being used increasingly in the USA to successfully combat the deadly C.diff.  Reminds me of how the evolution of fungi into penicillin has saved the lives of so many since it's introduction. 

Antibiotics are powerful in their ability to kill bacteria, but the problem is that friendly bacteria are also killed.  Fecal transplant appears to restore the normal balance.  One wonders if down the track fecal transplant will be used in some modified way to negate these harmful effects of antibiotics.

"Drugmakers racing to develop medicines and vaccines to combat a germ that ravages the gut and kills thousands have a new challenger: the human stool.

For patients hit hardest by the bacterium Clostridium difficile, getting a "stool transplant" could become a standard treatment within just a few years. Just as blood banks and sperm banks are now commonplace, stool banks may soon dot the landscape.

About 3 million Americans are infected annually with the bacterium - also known as C. diff - which spreads mainly through hospitals, nursing homes and doctors' offices. It is common in Australia in various strains, including the deadly 244.

Most people have no symptoms, but 500,000 Americans - more than half of them 65 and older - develop abdominal cramps, fever, diarrhea and inflamed colons. As many as 30,000 die each year from the bacterium, usually after recurrences of infection.

 

The infections are typically the result of taking antibiotics, which wipe out friendly bacteria in the colon that normally keep C. diff under control. Transplants of stool from screened donors - given by enema, colonoscopy or a tube down the throat - restore these bacteria.

Although the vast majority of C. diff infections occur in healthcare settings, more and more cases are occurring in younger adults and children who have not recently taken antibiotics or been hospitalised. They include people who take proton pump inhibitors - a leading class of heartburn drugs.

Costly treatments from Merck & Co and other drugmakers, and a vaccine from Sanofi, are on the horizon. But growing numbers of gastroenterologists are more excited about the use of human stool transplants, which in experimental settings have consistently cured 85 percent to 90 per cent of patients who have had multiple episodes of C. diff.
"Until recently, fecal transplants have been on the fringes of mainstream medicine," said Dr Cliff McDonald, an epidemiologist with the US Centers for Disease Control and Prevention. "It could become the primary mode of therapy within a year or two for patients with multiple recurrences."

Wheel of misfortune
The first recorded stool transplants were given in 1958 to four patients with inflamed colons. The procedures won more attention in the mid-1980s, when Australian gastroenterologist Thomas Borody began using them to treat his C. diff. patients.

Dr Moshe Rubin, head of gastroenterology at New York Hospital Queens, said most patients prefer the simplicity of a pill or injection, but for those with multiple bouts the fecal transplants could become a mainstay treatment.

"This has to be tested in large numbers of people before you unleash it for such a widespread disease," Rubin said.

C. diff medicines and vaccines could eventually claim total annual sales of $2 billion, according to Morningstar analyst David Krempa, or 10 times current sales.
Fecal transplants might initially be appropriate for patients who have had a third recurrence - or about 25,000 Americans each year, according to Dr. Sahil Khanna, a Mayo Clinic gastroenterologist. That number could rise as the procedure becomes more widely accepted, and pose perhaps the biggest threat to sales of Merck's experimental drug, which is expected to target a similar patient group.

About 90 per cent of C. diff patients initially treated with vancomycin, and 60 percent of those treated with another standard oral drug called metronidazole, recover within weeks. But 20 percent suffer recurrences, as surviving bacteria spores become activated or as patients become re-infected with spores that cling to clothing and furniture and can survive for months.

With each recurrence, risk of another rises, with more weight loss, diarrhea and fatigue. After a third recurrence, the risk of suffering a fourth is 60 per cent to 70 per cent.
"It's a constant wheel of misfortune," said Eric Kimble, a senior executive for Cubist Pharmaceuticals Inc, which is developing a C. diff treatment called CB-315.

Getting over the 'ick' factor
Fecal transplants have proved a godsend to such patients. They are given to those who have not benefited from metronidazole or vancomycin - or who have suffered repeat recurrences of C. Diff after being temporarily helped by the treatments.

In more than 100 of the experimental procedures performed by Dr Christine Lee, the transplants cured the infections and prevented recurrences in 90 percent of patients, said the infectious disease physician at St Joseph's Healthcare (hospital) at McMaster University in Hamilton, Ontario.

"Their energy level and appetite bounce back within a week, sometimes within 48 hours," Lee said. "They can't believe how simple and effective the procedure is."

In a five-minute bedside procedure, Lee introduces about 50 grams (1.75 ounces) of donated fecal matter into the rectum, using an inexpensive plastic plunger. A single procedure re-establishes the balance of bacteria.

Friends and family of patients, as well as doctors and nurses, provide without pay the stool used in Lee's procedures. They are screened to ensure they do not have viruses, such as HIV or hepatitis C, or other pathogens that can be transmitted to patients. She said some donate stool on a regular basis, which can be used for a great number of patients.

Once transplants are approved by health regulators, Lee predicted, enema procedures will be less costly than two other delivery methods now used for stool transplants. They include colonoscopy, in which doctors sedate the patient and insert stool into the colon, or through a different procedure in which a plastic feeding tube is passed through the nose, down the throat and into the stomach.

In the meantime, gastroenterologists say doctors and hospitals can help prevent C. diff by being more restrained in the use of antibiotics and ensuring that hospital rooms are diligently cleaned with bleach wipes to kill C. diff spores.

Dr Mark Pochapin, director of gastroenterology at NYU Langone Medical Center, said fecal transplants had more appeal than emerging anti-toxin approaches.

"They appear effective, balance the normal intestinal flora, are inexpensive and are safe when done with appropriate testing," he said. "They will far and away revolutionise how we treat this disease."

Many patients might benefit most from transplantation of their own stool, rather than relying on donors. They would include those undergoing chemotherapy or hip or knee replacements, all of which involve use of antibiotics, said the CDC's McDonald.
People, he said, would set aside stools for processing into capsules that would be frozen and stored until needed.

Such "bacterial treatment" after antibiotics might eventually also lower the risk of developing asthma, allergy, obesity or other conditions that may be partly linked to loss of helpful bacteria, McDonald said.

"Look at it as a way to put people's bacterial population back together again after antibiotics, like restoring Humpty Dumpty," said McDonald."


http://www.smh.com.au/world/science/blood-bank-sperm-bank--stool-bank-20121203-2aqqc.html

Dr Tom Borody Video Fecal Microbiota Transplant for Clostridium Difficle

Professor Tom Borody, on ABC TV Australia, Catalyst, Thursday, 14 July 2011 talks about Fecal Microbiota Transplantation (FMT) also known as "human probiotic infusion" for treatment of clostridium difficlile (c-diff).  He is the pioneer and leading world expert on FMT.

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