When the standard treatment for Clostridium difficile infection (CDI) – which includes an antibiotic course of either metronidazole or vancomycin – fails to eradicate the offending bacterium, physicians currently have few options for treating their patients. Sadly, standard treatment fails to resolve CDI for 15-26% of patients.1 When a physician prescribes one of these antibiotics a second time due to a recurrence of CDI, it is ineffective 40% of the time and continues to become less effective with each subsequent recurrence.

The most notable symptom of CDI is debilitating diarrhea. It occurs after a disruption in the normal (balanced) gastrointestinal tract microbiome, when pathogenic Clostridium difficile (C. difficile) bacteria are able to flourish, usually due to the use of broad-spectrum antibiotics, which destroy the beneficial bacteria in the gut. For vulnerable individuals, such as the elderly or those who have compromised immune systems, CDI can lead to death.


Proven in Practice

As we described in the Inside Tract®, issue 184, Health Canada approved a promising, targeted antibiotic called fidaxomicin (Dificid®) for the treatment of recurrent CDI. In May 2014, at the 24th European Congress of Clinical Microbiology and Infectious Diseases, researchers reported on a one-year study in the UK that found Dificid®, as a first-line treatment, to be clinically effective for the full resolution of CDI. The study also found that the use of Dificid® saves health care costs, compared to when metronidazole or vancomycin are administered as first-line treatments. In addition to this welcome, proven, treatment option, Canadian hospitals are improving their cleaning procedures and researchers are working to develop further approaches against this superbug.


Making Small Steps

Current research into innovative treatments for CDI is focusing on improving the bacterial diversity in the gut so that these beneficial bacteria can fight off the infection without the need for antibiotics and help prevent recurrences. These developing advances, described below, represent new hope in the battle against CDI, but keep in mind that this is still considered preliminary research.


Fecal Transplants

New research demonstrates the effectiveness of transplanting healthy donor stool into the colons of individuals infected with C. difficile.1 Previous studies involving hundreds of patients have shown that fecal transplant, performed through a variety of methods, is effective for curing recurrent CDIs, but this study from the Netherlands is the first randomized controlled trial, which the research community considers the most reliable type of study.

This study included 32 adult patients who were experiencing a relapse of CDI after at least one standard course of antibiotics. Of the 16 patients who received a fecal transplant, 13 of them achieved cure. The remaining 3 patients in that group received a second infusion of stool from a different healthy donor and 2 of them experienced cure. Only 4 patients in the vancomycin group experienced cure.

The diversity of microbiota present in the stool of patients treated with the fecal infusion during follow-up was similar to that of their donors, suggesting that the intestinal microbiota sustains a healthy diversity of good bacteria long after the initial fecal transplant.

Fecal transplants are not widely available and more research is required, as this study had only a few participants. In media reports, the authors of this study also say that they don’t believe direct fecal transplants are the final solution, but that innovative treatments, likely arising from further research, bring hope of an effective treatment for this devastating illness.2



One family member of a patient in Victoria, BC who suffered from a recurrence of CDI contacted the GI Society describing how the patient was able to access fecal transplant treatment. OpenBiome (www.OpenBiome.org), a non-profit organization based in the United States, provides physicians with highly screened fecal microbiota preparations in ready-to-use formats for fecal transplant treatment. The material they supply is available in different forms, depending on the preferred treatment route: colonoscopy, naso-gastric tube, enema, or capsules taken by mouth.

Under Health Canada’s personal use regulations, physicians in Canada can help patients legally obtain a three-month supply of OpenBiome’s fecal transplant material. The patient is responsible for the cost of this treatment, which is currently about $500US, including shipping. For physicians who wish to perform fecal transplants, OpenBiome is a safe, convenient alternative to finding and screening appropriate donors themselves. It is important to keep in mind, however, that very few Canadian physicians perform fecal transplants because it is still such an experimental treatment. The family member we spoke to said that the product arrived frozen had to be stored in a -20oC freezer in order to remain viable for up to 6 months.


RePOOPulate – Studied in Only Two Patients

In Ontario, researchers have taken the concept of a fecal transplant and developed a more patient-friendly stool substitute that they call RePOOPulate, in a play on the word ‘repopulate’. Three challenges that face fecal transplant therapy are concerns about the possible transmission of pathogens from donors’ stool, patient repulsion of the therapy (i.e., the ‘ick’ factor), and the fact that it is not possible to standardize a fecal transplant the way we normally do with medicines. The researchers conducted a very small pilot study, which included just two elderly women, but its findings are nonetheless optimistic.3

The researchers identified thirty-three beneficial bacterial strains from the stool of one donor, a healthy 41 year-old woman. They then grew (cultured) each of those strains using a lab system they developed that imitated the oxygen-free conditions in a human’s large intestine. The researchers made the RePOOPulate formulation by mixing these beneficial bacteria with sterile saline and performed the infusion therapies on the two study subjects within 24 hours of production.

The two subjects were each experiencing recurrent bouts of CDI after several rounds of vancomycin and the stool of both women contained the same highly infective strain of C. difficile. Both women were symptom-free six months after treatment.

The researchers suggest that no single bacterial strain is responsible for the success of the stool transplantation, as the strains appear to thrive best as a mixed community of beneficial bacteria.

The study authors say their research shows that a stool substitute might eventually be a feasible alternative to a human fecal transplant. Some of the researchers from this study are experimenting with the development of a time-released capsule containing a freeze-dried version of the mixture, which patients could take orally.4

Studies like this are encouraging, but much more research and development is required before treatments like these will be available.



The GI Society has heard from dozens of individuals whose stories were remarkably similar to those of the study participants above – repeated recurrence of CDI. However, we must consider that each patient is unique and might not respond in the same way as another individual to the same treatment. The advanced targeted antibiotic, Dificid®, is available in Canada, giving physicians another option for patients today who have recurrent CDI. Someday, additional treatment options, such as some form of transplantation of beneficial bacterial cultures, might finally give the health care community the upper hand in this ongoing battle against Clostridium difficile infection.

Sniffing out C. difficile

Diagnosing and treating CDI might become much simpler in the future. Researchers are working on an “electronic nose” that could detect C. difficile, most likely using stool samples, and even differentiate between various strains of the bacterium. A quick diagnosis is very important for effective treatment and eradication of the bug.

First published in the Inside Tract® newsletter issue 191 – 2014
1. Nood, E van et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. The New England Journal of Medicine. 2013;368(5):407-15.
2. Media Release. Fecal transplants cure most cases of C. difficile: Randomized controlled trial shows treatment works. The Canadian Press. 2013-01-17.
3. Petrof EO et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome. 2013;1 (3).
4. Ubelacker, S. Fake poop ‘RePOOPulate’ could replace real stuff to treat C. difficile. The Canadian Press.2013-01-08.