Fecal transplants vs. antibiotics: LMP researcher investigates the best method to treat C. difficile.

Sunday, March 17, 2013
Professor Susan Poutanen
Professor Susan Poutanen, Microbiologist and Infectious Disease Consultant, in her lab at Mount Sinai Hospital.

It’s been a hot news item lately – fecal transplants as the miracle cure for persistent, costly and often deadly C. difficile infections. While some recent studies are promising, the Department of Laboratory Medicine and Pathobiology’s Professor Susan Poutanen (MD, MPH, FRCPC), and lead researcher Professor Susy Hota of the Department of Medicine (MD, MSc, FRCPC), believe that their study will prove whether this unusual therapy is truly effective.

As one of the most common hospital-acquired infections, C. difficile affects thousands of Canadians per year. It’s an opportunistic bug. When broad-spectrum antibiotics disrupt a patient’s intestinal bacteria, it moves in to produce severe diarrhea, abdominal pain, vomiting, colitis and sometimes death. While targeted antibiotics such as vancomycin are used to treat this infection, they are not necessarily effective at preventing recurrences.

Prof. Poutanen explains how this normally acute condition can become chronic, “I have a whole new respect for C. difficile since I’ve been working with patients who are enrolled in this study. I’ve always warned patients whenever I’ve prescribed antibiotics that there can be various complications – one being C. difficile.” She continues, “But now I emphasize the potential for C. difficile even more after seeing the impact of this organism on patients’ lives, knowing that one bout of C. difficile may end up being a second bout 30 per cent of the time and a third or fourth bout up to 50 per cent of the time thereafter.”

The impact of the disease is apparent, “I’ve met patients on their fifth, sixth and seventh relapse who have become dependent on vancomycin. Every time they stopped the vancomycin they would relapse, and the old and frail frequently would have to be hospitalized each time.”

Fecal TransplantFor many desperate patients who have become reliant on expensive antibiotics, fecal transplants are a viable option with reported success rates between 80 and 90 per cent. The procedure involves taking stool from a healthy donor and transplanting it into a patient. It has shown promise based upon a recent study published in the New England Journal of Medicine. In addition, researchers at Guelph University have been experimenting with developing synthetic stool for this type of procedure. The theory behind fecal transplants is that the healthy stool, containing a wide variety of bacteria, will keep C. difficile in check.   

In the first North American randomized controlled trial of its kind, Profs. Poutanen and Hota are comparing fecal transplants to the standard treatment: a steadily decreasing or “tapering” dose of vancomycin. Unlike similar transplant studies, that have used more costly and invasive methods, this study uses enemas which are practical and can be widely adopted.

Initiated in August 2010, the study is a non-blinded, randomized controlled trial involving patients with recurrent C. difficile infection. Patients receive either a vancomycin taper or a fecal transplant and are then followed for 120 days to see if the infection reoccurs. If patients do relapse after taking the vancomycin taper, they are then offered the fecal transplant option.

One of the challenges of the study was to get approval from Health Canada. “Health Canada treated it like an organ transplant in one aspect and as a pharmaceutical in another aspect,” says Prof. Poutanen. This approval was key to the design and protocol of the study to ensure patient safety.

While Professor Susy Hota and other researchers, including Professors Donald Low, Dylan Pillai and Allison McGeer from the Department of Laboratory Medicine and Pathobiology, initiated the project, it is Prof. Poutanen’s unique experience in medical microbiology and infectious diseases that allowed her to devise how the transplant material should be collected, delivered to the laboratory, processed in the laboratory, and delivered to the study team to administer to the patient. Prof. Hota describes this unique combination of laboratory and clinical experience, “Dr. Poutanen has been instrumental to the study. On the lab-side, it is important to screen donors and to manufacture the product. She also helped to define the standard operating protocol for the study so that it runs smoothly. In addition, she also covered the clinical side of the study during my maternity leave.”

Professors Poutanen and Hota anticipate that there may be other exciting applications for this procedure, such as in patients with Inflammatory Bowel Disease. “The microbiome and the impact of the microbiome on all diseases is an incredibly hot topic,” Prof. Poutanen says, “so even though Inflammatory Bowel Disease is not understood as an infectious disease per se, fecal transplants may have a role in treatment. We have been discussing potentially expanding into that realm.”

Are fecal transplants the panacea for C. difficile? Prof. Poutanen believes that the procedure is very promising but has yet to be proven, “The goal in my mind for this trial is to definitively understand whether this in fact does work better than the vancomycin taper. If it doesn’t, then we don’t want to give false hope to patients and, if it does, that’s fantastic – let’s make this a standard therapy that can be adopted by other labs and clinical teams.”

Click here for more information on the study.