1. Duodenal Infusion of Donor
Feces for Recurrent
Clostridium difficile
The New England Journal of Medicine
January 31, 2013
Debi Armbruster
2. Hypothesis
• The effect of duodenal infusion of donor feces in patients with recurrent C.
difficile infection will be more effective for treatment than antibiotic therapy,
Vancomycin, both with and without bowel lavage.
Questions:
• Experience is limited
3. Study Design
• Open label, randomized, controlled trial
• 3 treatment regimens
• Infusion of donor feces preceded by an abbreviated regiment of Vancomycin and
bowel lavage
• Standard Vancomycin regimen
• Standard Vancomycin with bowel lavage
4. Infusion of Donor Feces
• Donors
• <60 years of age
• Screened using a questionnaire addressing
• Risk factors for transmissible diseases
• Screened for parasites
• Blood screening
• Donor pool created and screening was repeated every 4 months
5. Study Design
• Independent Variable: Duodenal infusion of donor feces
• Dependent Variable: Recurrent C. difficile infection
7. Exposures and Outcomes
• Primary end point: Cure without relapse within 10 weeks after initiation of
therapy
• Secondary end point: Cure without relapse after 5 weeks
• Bacterial diversity: Simpson’s Reciprocal Index of diversity, scale ranging
from 1-250
***higher the score higher the diversity
8. Study population
• At least 18 years of age
• Life expectancy of at least 3 months
• A relapse of C. difficile infection after at least one course of adequate antibiotic therapy
• > 10 days of Vancomycin >125 mg 4 times a day
• >10 days of Metronidazole 500 mg 3 times per day
• Exclusions:
• Prolonged compromised immunity due to chemotherapy, HIV, prolonged use of prednisolone
• Pregnancy
• Use of antibiotics other than for treatment of C diff
• Admission to an ICU
• Need for vasopressor medication
9. Results
• Donor feces
• Cured 15 of 16 patients (94%)
• Vancomycin
• Resolution 4 of 13 patients (31%)
• Vancomycin with bowel lavage
• Resolution 3 of 13 patients (23%)
10. Critique
• Alternative interpretations
• “first line therapy”
• Additional Controls
• Amount of feces
• Potential routes of infusion
• Cofounders
• Massachusettes Medical Society
• Netherlands Organization for Health Research and Development
11. Final Remarks
• Nutritional Recommendations for C. difficile:
• The use of probiotics found in fermented foods or over-the-counter probiotic
supplement.
• Soft foods diet
• Avoiding nuts, seeds, foods high in fiber, and gas-producing
• Easy to chew
• Protocol for standard of practice
12. References
• M.D., E. N. Duodenal Infusion of Donor Feces for Recurrent Clostridium
difficile. The New England Journal of Medicine, 368, 407-415.
Introduction: Why did you choose the article?
Soo interesting
I think the bacteria in the intestines is so cool
They call this a “transplant” because they are taking something from someone else and it’s regrowing in another person’s body.
I wanted to present on something that actually showed significant results
: Between 1996 and 2009, C diff rates for hospitalized people over the age of 65 increased 200%, according to the latest data from the CDC. As age increased, so did the risk of infection.
Explain the clinical relevance- why YOU think article is relevant
C. difficile infections are the most common cause of pseudomembranous colitis, and in rare cases this can progress to toxic megacolon, which can be life-threatening.
Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system, with costs of 3.2 billion dollars annually
Primary risk factors are exposure to antibiotics, exposure to a healthcare environment, and acid suppressing medications
Vancomycin delivered orally (125 mg four times per day) plus intravenous metronidazole (500 mg three times a day) is the treatment of choice in patients with severe and complicated CDI who have no significant abdominal distention
C difficile infection was defined as diarrhea (>3 loose or watery stools per day for at least 2 consec days or > 8 loose stools in 48 hours) and a positive stool test for C difficile toxin.
Introduction: Why did you choose the article?
Explain the clinical relevance- why YOU think article is relevant
Bowel lavage flushes out the entire intestinal tract to prepare for medical imaging studies and surgery. It can also be used in the treatment of some kinds of poisoning. In this procedure, patients drink a large quantity of liquid which moves through the intestines. The volume of fluid exceeds the absorption capabilities of the bowel, causing diarrhea which will eventually run clear, once everything in the intestines has been expelled.
Assumed:
Cure rate of 90% with donor feces infusion
Cure rate of 60% with antibiotic therapy
Abbreviated regimen:
Vancomycin (500 mg orally 4 times a day for 4 or 5 days)
Followed by bowel lavage with 4 liters of macrogol (Klean-prep) solution on the last day of antibiotic treatment
And the infusion of a suspension of donor feces through a nasoduodenal tube the next day
Standard Vancomycin regimen:
500 mg orally 4 times a day for 14 days
Standard Vancomycin regimen with Bowel Lavage
Bowel Lavage on day 4 or 5
**If C diff recurrent development after the first donor feces was give a second infusion with feces from a different donor.
**Patients who antibiotics failed were offered treatment with donor feces off protocol
*** Donor pool created and screening was repeated every 4 months
***Before donation, anther questionnaire was used to screen for recent illnesses
**Feces collected by donor on the day of infusion and immediately transported to the hospital
-Feces were diluted with 500 ml of sterile saline
-solution was stirred, strained, and poured in a sterile bottle
-within 6 hours after collection, solution was infused through a nasoduodenal tube (2-3 min per 50 ml)
-tube removed 30 minutes after infusion, patient were monitored for 2 hours.
Adverse events:
Immediately after donor feces infusion
-94% of patients had diarrhea
-31% had cramping
-19% had belching
**symptoms subsided in 3 hours after treatment
** no other adverse effecs related to study treatment
Looked at this treatment because antibiotic therapy failure rate is very very high.
Primary end point: cure without relapse within 10 weeks after initiation of therapy
Secondary end point: cure without relapse after 5 weeks
- patients in infusion group who required a second infusion of donor feces
Relapse: diarrhea with a positive stool test for C. difficile toxin
Fecal microbiota for bacterial diversity by extracting DNA from samples from patients before and after donor-feces infusion and from respective donor samples
Extracted DNA from before and after donor-feces infusion and from the respective donor samples.
-estimated diversity of the bacterial communities before and after donor feces infusion using Simpson’s Reciprocal Index of diversity, scale ranging from 1-250
***higher the score higher the diversity
Primary end point: cure without relapse within 10 weeks after initiation of therapy
Secondary end point: cure without relapse after 5 weeks
- patients in infusion group who required a second infusion of donor feces
Relapse: diarrhea with a positive stool test for C. difficile toxin
Fecal microbiota for bacterial diversity by extracting DNA from samples from patients before and after donor-feces infusion and from respective donor samples
Mainly elderly patients, highly prevalent
43 patients
17- donor-feces infusions
13- vancomycin
13- vancomycin + bowel lavage
13 out of 16 patients in the infusion group were cured after the first infusion of donor feces (81%)
2 out of the 3 were cured after 2nd infusion
**overall donor feces cured (94%)
*donor feces infusion was statistically superior to both vancomycin regimens
* Overall cure rate ration of donor-feces infusion was 3.05 vs. vancomycin alone
-1 out of 16 patients in the infusion group with recurrence of infection (6%)
-8 out of 13 patients in the Vancomycin group with recurrence ( 62%)
-7 out of 13 patients in the Vancomycin group +bowel lavage ( 54%)
Statistically superior to Vancomycin with and without bowel lavage
Looking at the fecal microbiota: Patients had major shift in microbiiota after donor-feces infusionn toward that of the donors.
Importance of the Results: kind of speaks for itself… patients
Why used in patients who have had relapse? Why not used in patients who have not experienced a relapse yet? The number of clinical physicians performing procedure are limited.
One of the exclusion criteria was patients admitted to the ICU who are critically ill, evidence with autoimmune diseases. I believe that another study should be done to look at these patients just because C diff infection in the ICU is associated with high death rates.
Structure or organ “gut microbiota” needs to be studied more with the different factors of: age, diet, presence of diseases
Also, the efficiacy of antibiotic therapy decreases with subsequent recurrences. So why not initiate treatement with donor-feces infusion after the second or third relapse?
Vancomycin efficacy was a lot lower than expected
Protocol is unknown for donor-feces infusion.
-amount of feces required and the importantance of varying potential routes of infusion are unknown
-many different treatement protocols?
Additional Controls
-Something that they mentioned that was unknown is the amount of feces and the route of infusion
-More research should be done on these 2 so proper protocols can be set for in practice use
Cofounders:
-Massachusettes Medical Society
-Netherlands Organization for Health Research and Development
If you have not done so already, the most important thing to introduce into your diet are *friendly bacteria*, often called probiotics, that will help repopulate your gut and crowd out the potential for regrowth of the C-diff bacteria.
-using probiotics results in a large reduction in C-diff associated diarrhea without an increase in adverse side effects
Introducing donor fecal microbiota will repopulate the gut and intestines with healthy diversity of good bacteria
