Tag Archives: C. diff. treatments

Fecal Microbiota Transplant – Study Provides Insight Into Structural/Metabolic Changes That Occur After FMT

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Fecal microbiota transplantation

The process of delivering stool bacteria from a healthy donor to a patient suffering from intestinal infection with the bacterium Clostridium difficile  works by restoring healthy bacteria and functioning to the recipient’s gut, according to a study published this week in mBio®, the online open-access journal of the American Society for Microbiology.

The study provides insight into the structural and potential metabolic changes that occur following fecal transplant, says senior author Vincent B. Young, MD, PhD, an associate professor in the Department of Internal Medicine/Infectious Diseases and the Department of Microbiology & Immunology at the University of Michigan in Ann Arbor. The transplants, which have been successful at curing more than 90 percent of recipients, have been used successfully since the 1950s, he says, though it hasn’t been clear how they work to recover gut function.

“The bottom line is fecal transplants work, and not by just supplying a missing bug but a missing function being carried out by multiple organisms in the transplanted feces,” Young says. “By restoring this function, C. difficile isn’t allowed to grow unchecked, and the whole ecosystem is able to recover.”

Young and colleagues used DNA sequencing to study the composition and structure of fecal microbiota (bacteria) in stool samples from 14 patients before and two to four weeks after fecal transplant. In 10 of the patients, researchers also compared stool samples before and after transplant to samples from their donors.

All transplant patients, treated at the Essentia Health Duluth Clinic in Minnesota, had a history of at least two recurrent C. difficile infections following an initial infection and failed antibiotic therapy.

Studying families of bacteria in the samples, investigators found marked differences among donor, pre-transplant and post-transplant samples. However, those from the donors and post-transplant patients were most similar to each other, indicating that the transplants at least partially returned a diverse community of healthy gut bacteria to the recipients. While not as robust as their donors, the bacterial communities in patients after transplant showed a reduced amount of Proteobacteria, which include a variety of infectious agents, and an increased amount of Firmicutes and Bacteroidetes bacteria typically found in healthy individuals, compared to their pre-transplant status.

Then, using a predictive software tool, researchers analyzed the relationship between the community structure of the micoorganisms and their function, presumably involved in maintaining resistance against CDI.

They identified 75 metabolic/functional pathways prevalent in the samples. The samples taken from patients before transplant had decreased levels of several modules related to basic metabolism and production of chemicals like amino acids and carbohydrates, but were enriched in pathways associated with stress response, compared to donor samples or post-transplant samples.

CDI has significantly increased during the past decade, Young says, with previous studies estimating there are more than 500,000 cases of CDI in the United States annually, with health care costs ranging from $1.3 billion to $3.4 billion. Up to 40 percent of patients suffer from recurrence of disease following standard antibiotic treatment. In a healthy person, gut microorganisms limit infections but antibiotics are believed to disrupt the normal structure of these microoganisms, rendering the gut less able to prevent infection with C. difficile.

Further identification of the specific microorganisms and functions that promote resistance of bacterial colonization, or growth, may aid in the development of improved CDI treatments, Young says: “If we can understand the functions that are missing, we can identify supplemental bacteria or chemicals that could be given therapeutically to help restore proper gut function.”

For article in its entirety click on the link below:

http://www.eurekalert.org/pub_releases/2014-06/asfm-ftr061214.php

 

The study was supported by the National Institutes of Health, the Michigan Gastrointestinal Peptide Research Center, and the Essentia Health Foundation in Duluth, Minn.

mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.

The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM’s mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

 

C. difficile Infection Treatment; DIFICLIR™ (fidaxomicin) Clinically Effective At Reducing Recurrence and Provides Cost Savings When Used First-Line

* In The News *  14 May 2014

 

DIFICLIR™  (fidaxomicin)

Recurrence has been identified by The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) as the most important problem in the treatment of CDI.[1]

New  data presented at the 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) demonstrates that fidaxomicin, when used first-line, is clinically effective and provides cost savings for the treatment of potentially fatal Clostridium difficile infection (CDI).[2] Treatment with fidaxomicin led to a reduction in recurrence for patients with CDI[2] and a saving of over £48,000 to the UK’s NHS versus standard of care treatment (vancomycin or metronidazole).[3]

The study, conducted at St George’s Hospital in London, England, is the first of its kind and looks at a year’s experience using fidaxomicin as a first-line treatment for all adults confirmed to have CDI, including populations not previously studied in randomised controlled Phase III   trials.[2],[4] Data collected from a total of 62 patients treated with fidaxomicin during the 12 month evaluation period were compared with those from a retrospective cohort treated with standard of care (vancomycin or metronidazole) during the previous 12 month period.[5]

Only 6% of patients treated with fidaxomicin had a recurrence of CDI, within 28 days of end of therapy, compared with a 20% recurrence rate with vancomycin/metronidazole in the preceding year.[5] Recurrence is a major challenge in CDI treatment, with previous studies reporting that patients who have already had one recurrence, have a 40% risk of a further episode of CDI.[6]Importantly, in this ‘real world’ study, there were no second recurrences reported in those treated with fidaxomicin. Hence, the observed reduction in recurrence rates and reduced hospital stays since the introduction of fidaxomicin as first-line treatment for CDI has culminated in overall cost savings.[5]

Commenting on the findings, Dr. Tim Planche, lead investigator and Consultant Microbiologist, St George’s Hospital said: “We decided to start using fidaxomicin first-line over a year and a half ago for all cases of Clostridium difficile infection at St George’s, after the exciting data reported in clinical trials showed reduction in recurrence of infection. Having looked at our data we are very pleased to see that we find the same effects occurring in our own “real world” patients. Our team have also looked at the cost-effectiveness of using fidaxomicin and we are assured of the cost benefits of continuing to use this drug. From our experience of using this drug we are very happy to continue using it first-line and that it is worth other hospitals considering as part of their strategy to treat and control Clostridium difficile infection.”

Based on the findings of this landmark study, The Drugs and Therapeutics Committee for the hospital have upheld their recommendation for the use of fidaxomicin as a first-line therapy for all adult patients with CDI.[5]

CDI is one of the most common causes of antibiotic-associated diarrhea and severe cases can lead to bowel surgery and even death.[7] Hospital patients with CDI are up to three times more likely to die in hospital (or within a month of infection) than those without CDI.[8],[9] Recurrence is a major challenge in CDI treatment, 25% of CDI patients suffer a recurrence within one month[10],[11],[12]and patients who have already had one recurrence have a 40% risk of a further episode of CDI.[6]

Commenting on the findings, Professor Oliver Cornely, University Hospital Cologne, Germany said: “One of the biggest challenges to optimal CDI management is recurrence, therefore the significant reduction in disease recurrence by fidaxomicin, compared with vancomycin, is an important step in reducing the morbidity and possibly mortality associated with CDI. The treatment for CDI had remained largely unchanged for 20 years. This real life data demonstrates a treatment advance that can improve patient outcomes and reduce the significant burden of this disease, which will hopefully lead to improved management of CDI in clinical practice.”

These results represent the interim findings of a larger cohort of real world data being collected and analysed from across the UK to assess the effectiveness of fidaxomicin. Data reporting from additional study centres are expected to be presented later in the year.

 

About Astellas Pharma Europe Ltd.

Astellas Pharma Europe Ltd., located in the UK, is the European Headquarters of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. As a global company, Astellas is committed to combining outstanding research and development (R&D) and marketing capabilities to continue to grow in the world pharmaceutical market. Astellas Pharma Europe Ltd. manages 21 affiliate offices located across Europe, the Middle East and Africa. In addition, the Company has an R&D site and three manufacturing plants in Europe. The company employs approximately 4,300 staff across these regions. For more information about Astellas Pharma Europe, please visit http://www.astellas.eu/.

References

1. Bauer MP, et al. European Society of Clinical Microbiology and Infectious Disease (ESCMID): treatment guidance document for Clostridium difficile-infection (CDI). Clin Microbiol Infect. 2009;15:1067-79.
2. Planche T, et al. Cost-effectiveness of fidaxomicin as first-line treatment for Clostridium difficile infection. Abstract presented at ECCMID 2014.
3. Astellas Data on File DIF14036UK.
4. Cornely A, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Diseases. 2012:12;281-289.
5. Astellas Data on File FDX/13/0090/EUi.
6. Kelly CP, LaMont JT. Clostridium difficile – more difficult than ever. N Engl J Med. 2008;359(18): 1932−1940.
7. Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol. 2011;8:17-26.
8. Oake N, et al. The effect of hospital-acquired Clostridium difficile infection on in-hospital mortality. Arch Intern Med. 2010;170:1804-10.
9. Hensgens MP, et al. All-Cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a Multicenter Cohort Study. Clin Infect Dis. 2013;56:1108-16.
10. Lowy I, et al. Treatment with Monoclonal Antibodies against Clostridium difficile Toxins. N Engl J Med. 2010;362;3:197-205.
11. Bouza E, et al. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhoea. Clin Micro Infect. 2008;14(Suppl 7):S103-4.
12. Louie TJ, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-31.
13. Poutanen SM, et al. Clostridium difficile-associated diarrhoea in adults. CMAJ. 2004;171:51-8.
14. Kelly CP, et al. Clostridium difficile infection. Ann Rev Med. 1998;49:375-390.
15. Crobach MJ, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): Data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Micro Infect. 2009;15:1053-1066.
16. Pepin J, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-7.

What you can do while experiencing symptoms of diarrhea

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What can you do while experiencing symptoms of diarrhea?
Liquids
Drink plenty of liquids between meals to avoid dehydration. Water, broth, gelatin, ices, and sports drinks are all good choices.
Room temperature
Some people tolerate liquids at room temperature better than those served hot or cold.
Sugar-free foods
Avoid sugar-free foods when you have diarrhea. The sugar alcohols used to sweeten these foods, such as sorbitol and xylitol, can worsen diarrhea.
Dairy products
Do not consume dairy products when symptoms are most severe. Add low-fat or fat-free milk back into your diet slowly.
Small meals
Have small meals and snacks, rather than big meals.
Bland foods
It is recommended that you choose bland foods when you have diarrhea.
Good choices include:
  • Applesauce
  • Bananas
  • Canned soft fruits
  • Cooked hot cereals
  • Crackers
  • Eggs
  • Mashed potatoes
  • Pretzels
  • Smooth nut butters
  • Soup
  • Toast
  • White rice
Foods to avoid
Do not choose foods that are greasy, fried, or fatty. Do not add butter, oil, or other fats to your foods. Certain foods tend to cause discomfort for many patients, including:
  • Beets
  • Broccoli
  • Brussels sprouts
  • Cabbage
  • Carbonated beverages
  • Cauliflower
  • Corn
  • Dried beans
  • Dried fruit
  • Fried or fatty meats
  • Greens
  • High-fiber breads
  • High-fiber cereals
  • Nuts
  • Onions
  • Raw fruits (except bananas and melon)
  • Raw vegetables
  • Whole grains
  • Whole milk
Grains
Choose grains that contain less than 2 grams of fiber/serving.
* CLEAR LIQUID DIETS are only to be followed for three (3) days.  If adequate
nutrition or hydration can not be maintained, please contact the Physician and health
care professionals promptly and seek medical attention.
Meats, chicken, and fish
Select lean meats, chicken, and fish.
Yogurt
Patients with diarrhea caused by antibiotics may benefit form adding yogurt to their diet.
When should the physician be notified?
Call your doctor if you:
  • Have mucus, blood, or pus in your stools
  • Have diarrhea lasting longer than 2 to 3 days
  • Have not urinated in 12 hours
  • Have severe pain or abdominal cramping
  • Are vomiting and experiencing diarrhea at the same time
  • Have a chronic illness, such as diabetes
  • Have a high fever (more than 101º F)
  • Are pregnant
  • Experience rapid breathing, fever, or dizziness
  • If you have traveled to a foreign country, or have taken an antibiotic recently or in the past two/three months, or have developed diarrhea upon your return from any visit out of your immediate area.
Remember to:
  • Eat and drink whatever you think will work best for you
  • Frequent hand-washing breaks and for a minimum of twenty (20) seconds, before exiting a restroom, before/after eating, before/after entering a patients room, before/after wearing gloves during patient care, after changing diapers, after grooming and handling pets and Wash  hands often.
  • Eat and drink small portions, gradually increasing your diet as tolerated
 
References and recommended readings
Eating hints before, during, and after cancer treatment. National Institutes of Health, National Cancer Institute Web site. http://www.cancer.gov/cancertopics/coping/eatinghints/page4#diarrhea. Accessed June 5, 2013.
Mayo Clinic staff. Diarrhea. Mayo Clinic Web site. http://www.mayoclinic.com/health/diarrhea/DS00292. Accessed June 5, 2013.
US National Library of Medicine, National Institutes of Health. Diarrhea. MedlinePlus Web site. http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm. Updated January 26, 2012. Accessed June 5, 2013.

Seeking Patients Who Have Had Three or More Recurrences With a C. difficile Infection

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3 April 2014

Dr. Tanvi Dhere, MD and Dr. Colleen Kraft, MD at Emory University are currently working with a company testing a set of encapsulated fecal transplants (to swallow) for treatment of recurrent C. difficile infection.  

The first phase (15 patients) has been completed and patients showed a good response.  The delivery is ideal for many patients with C. difficile infection who are elderly and with multiple comorbidities who may have difficulty with colonoscopy.  

We are looking for patients who are on their third or more recurrence of C. difficile infection.

Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) are ineligible.

 If you have any potential patients, please have them contact Dr. Colleen Kraft at 404-712-8889 (USA) or email:   colleen.kraft@emory.edu.

*Patients please contact Dr. Colleen Kraft directly via: email for additional information and consideration.  Also,  participants must be willing to travel to Atlanta for 4 study visits

Thank you.

Photo courtesy of E. Ford