Tag Archives: FMT Information

Fecal Microbiota Transplantation From A Donor To Treat Recurrent C.difficle Infection

Fecal microbiota transplantation (FMT) from a donor (heterologous) to treat recurrent Clostridium difficile infection (CDI) is safe and more effective than self (autologous) transplantation, according to data from a randomized controlled, double-blind clinical trial.

However, the results, published online August 23 in the Annals of Internal Medicine, also show that the treatment success rate in the control group varied substantially between two study locations, which suggests there are subtleties not yet understood with the approach.

The efficacy of FMT using donor stool to treat recurrent CDI has made headlines, but so far it has largely been tested only in open-label clinical trials and case series.

 

To complement these studies, Colleen R. Kelly, MD, from the Women’s Medicine Collaborative, The Miriam Hospital, Providence, Rhode Island, and coworkers enrolled 46 patients who had had at least three recurrences of CDI and who were treated with vancomycin for the most recent infection and randomly assigned them to receive donor or self stool preparations by colonoscopy.

The researchers assessed adverse events for 6 months after FMT, defining efficacy as cessation of diarrhea without the need for further antibiotics during the 8 weeks after the intervention. All stool was subject to microbiota analysis before and after FMT.

Twenty of the 22 patients in the donor FMT group (90.9%; 95% confidence interval [CI],69.2% – 97.8%) were clinically cured compared with

15 of the 24 (62.5%; 95% CI, 41.6% – 79.6%) patients who received self FMT (P = .042).

The nine patients who developed CDI after self FMT were then given donor FMT and were cured.

Microbiome analysis revealed no improvement in gut microbial diversity after self FMT, but restoration of a normal microbiota with donor FMT, including increases in Bacteroidetes and Firmicutes and decreases in Proteobacteria and Verrucomicrobia populations.

An unexpected finding was that patients treated autologously at Montefiore Medical Center in the Bronx, New York had a much higher cure rate than those treated autologously at The Miriam Hospital in Providence. Specifically, for Rhode Island, cure rate with donor FMT was 90.0% (CI, 51.8% – 98.7%) vs 42.9% (CI, 20.1% – 69.0%) with self FMT. For New York, cure rate with donor FMT was 91.7% (CI, 57.2% – 98.9%) compared with 90.0% (CI, 51.8% – 98.7%) with self FMT.

The researchers list clinical differences among the patients at the two sites that could explain the different responses to self FMT:

  • NY patients were infected longer, had more recurrences, and had more courses of fidaxomicin than did Rhode Island patients.
  • NY patients waited longer to be treated and took antibiotics longer before entering the study, and may have been cured at that time.
  • Fecal microbiomes among NY patients had more Clostridia species, which may have occupied niches for C difficile.

Limitations of the study include lack of inclusion of baseline antibody titers and infection severity, small sample size attributed partly to unwillingness of participants to risk assignment to the autologous group, and nonuniform stool doses. In addition, the researchers mention that some patients may be infected according to polymerase chain reaction (PCR)-based identification of the pathogen, but be asymptomatic, and that some patients may have diarrhea resulting from undiagnosed irritable bowel syndrome but also be infected with C difficile, according to PCR testing.

In an accompanying editorial, Elizabeth L. Hohmann, MD, from Massachusetts General Hospital in Boston, points out another limitation, that “the population enrolled in this trial was younger (mean age, 50 years) and seemed healthier and more adventurous than most patients with recurrent CDI.” In contrast, about 60% of her patients with whom she discusses FMT are older than 60 years, and 30% are older than 75 years. However, the investigators had to recruit patients younger than 75 years to comply with FDA regulations to consider FMT as an investigational new drug.

No serious adverse events were reported. The researchers conclude, “FMT using fresh donor stool administered via colonoscopy after a course of vancomycin was effective at preventing further CDI episodes in patients with multiply recurrent infection.” They call for additional investigation to identify types of patients most likely to benefit from FMT using donor stool.

Dr Hohmann regards the differing response rates to autologous FMT at the two study sites as instructive, underscoring the value of conducting a rigorous controlled trial even when the tested technology has proven itself in other types of investigations. “Their results prompt us to ask again whether microbial manipulation has any as-yet unappreciated health benefits or risks and whether there are preferred microbiomes for specific human populations or locales,” she concludes.

To read this article in its entirety:

http://www.medscape.com/viewarticle/867727?nlid=108986_2981&src=wnl_dne_160823_mscpedit&uac=206986BK&impID=1183588&faf=1

 

Clostridium difficile (C. diff. ) Review: Early Diagnosis, Prevention, and Treatment

C. difficile Review: Early Diagnosis, Prevention, and Treatment

March 2016

NewsSpeaker

An update on the 2011 comparative effectiveness review on the early diagnosis, prevention, and treatment of Clostridium difficile was released to aid healthcare professionals, patients, policymakers, and others in well-informed decision-making.Researchers aimed to highlight the differences in accuracy of diagnostic tests and the effects of interventions to prevent and treat C. diff infection (CDI) in adults. Data was analyzed from searches in Medline, the Cochrane Clinical Trials Registry, and Embase from 2010–April 2015 as well as referenced studies and recent systematic reviews.Studies for inclusion looked at sensitivity and specificity for diagnostic tests in at-risk patients for CDI. Randomized controlled studies or high-quality cohort studies that evaluated adults with CDI or suspected CDI for treatment interventions were included. A total of 37 diagnostic studies and 56 prevention or treatment intervention studies were included for the review update.

RELATED: 6 Antibiotic-Resistant Threats Examined in CDC’s New Superbug Report

High-strength evidence indicated that nucleic amplification tests were sensitive and specific for CDI when cultures were used as the reference standard. High-strength evidence also showed that in treating CDI, vancomycin was more effective than metronidazole and the effect did not vary by severity (moderate-strength).

Fidaxomicin remained noninferior to vancomycin for initial CDI cure (moderate-strength) but proved superior in the prevention of recurrent CDI (high-strength).

Low-strength evidence suggested that fecal microbiota transplantation (FMT) may exert a significant effect on reducing recurrent CDI. In addition, lactobaccilus strains and multiorganism probiotic can also reduce recurrent CDI. Saccharomyces boulardii, however, did not prove more effective than placebo in the prevention of recurrent CDI.

The review was prepared by the Minnesota Evidence-based Practice Center for the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

 

To access the .pdf report format please click on the link below:

https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2208

 

To read the article in its entirety please click on the link below:

http://www.empr.com/news/updated-review-includes-new-c-diff-diagnosis-treatment-guidance/article/486399/

Patient and Healthcare Provider Information For Fecal Microbiota Transplantation (FMT)

For patients searching for physicians participating in  Fecal Microbiota Transplantations

The American Gastroenterological Association (AGA) website hosts a complete page with

full coverage and information pertaining to this subject.

Please click on the link below to be directed to the AGA website to assist you.  Thank you

http://fmt.gastro.org/find-a-practitioner/

 

Note:  This treatment – in any form – has not yet been approved by the
U.S. Food and Drug Administration (FDA).

Clinical data is pending and FMT remains investigational at this time

and Clinical studies are in progress.

For updates visit the US Food and Drug Administration website:

http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vaccines/ucm387023.htm

C. difficile; Fecal Microbiota Transplant (FMT) for C. diff Colitis

cdiffFMTimage

FMT for C diff colitis: How to introduce FMT

Fecal Microbiota Transplantation (FMT), commonly called fecal transplant, is the most effective intervention known for chronically relapsing, antibiotic resistant C diff colitis. There are many ways to introduce donor fecal microbiota to a C diff infected colon. Different methods of performing the transplants include enema, colonoscope, nasogastric tube, and encapsulation.
Two research groups have investigated the most common ways to introduce FMT, and how effective they are compared to each other. The first group was Ethan Gough et al. in the November 2011 article “Systematic Review of Intestinal Microbiota Transplantation (Fecal Bacteriotherapy) for Recurrent Clostridium difficile Infection” published in the journal Clinical Infectious Diseases. Here’s what they found:

• Of 72 C diff colitis patients given FMT by gastroscope or nasojejunal tube, 72.8% were cured without relapsing.
• Of 62 C diff colitis patients given FMT by colonoscope, 83.3% were cured without relapsing.
• Of 156 C diff colitis patients given FMT by enema or rectal catheter, 92.3% were cured without relapsing.

Similarly, Zain Kassam et al., in their April 2013 article “Fecal Microbiota Transplantation for Clostridium difficile Infection: Systematic Review and Meta-Analysis” found that lower GI FMT (enema, rectal catheter, colonoscope) led to a 91.2% resolution rate, while upper GI FMT (gastroscope, naso gastric or nasojejunal tube) led to an 80.6% resolution rate.
Lastly, Canadian infectious disease doctor Thomas Louie presented a poster called “Fecal Microbiome Transplantation (FMT) via oral fecal microbial capsules for recurrent Clostridium difficile infection (rCDI)” at the Infectious Disease Week in October 2013. The poster described preparing a fecal slurry like the type used for enema, colonoscope, or gastroscope instillation, then using serial centrifugation to extract the bacterial portion and triple encapsulating that. At that time, he reported a 27/27 cure rate with no significant side effects. So far in my practice, I have found the encapsulation method to be safe and effective as well.

Dr. Mark Davis, ND, Chairperson Fecal Microbiota Transplant Committee

May 2014