Fecal Microbiome Transplant in Capsule Form

October 7, 2013

Clostridium difficile colitis can be cured by having patients swallow capsules brimming with other people’s concentrated stool. Inexpensive, effective, and readily available. This could be an enormous opportunity for primary care (if the FDA approves it).

“We have to get over our yuck factor,” declares Thomas Louie, MD. This is a man who knows what he is talking about, because his results show that Clostridium difficile colitis patients can be cured by having them swallow capsules brimming with other people’s concentrated stool. Inexpensive, effective, and readily available-this could be an enormous opportunity for primary care (if the FDA approves it). There’s nothing specialty-focused about this methodology, which I’ll get to in a moment (although someone needs to assemble those capsules).

During a presentation on October 3, 2013, at IDWeek 2013 in San Francisco, Dr Louie made a compelling case for what many of us already know-that fecal microbiome transplant (FMT) is far superior to antibiotics in the treatment of recurrent C difficile infection (rCDI). Most centers report >90% cure rates, compared with dismal cure rates for repeated antibiotics. Despite the availability of what Dr Louie called “a life-changing” therapy, FMT remains underused in the United States. He presented a new approach that is likely to be more acceptable-less yucky-to most patients.

According to Dr Louie, a professor of infectious diseases and microbiology at the University of Calgary in Alberta, the research began as an approach to patients who could not tolerate traditional delivery modes for FMT. Dr Louie described a woman who was unable to hold enemas for FMT, and for whom a nasogastric tube was unacceptable because of esophageal varices. To treat her, he developed a methodology for the concentration of donor fecal bacteria into capsule form, for oral administration.

He dismissed the “yuck factor,” provocatively labeling it as a holdover from schoolyard embarrassments. Even among physicians, he feels that this has impeded rapid transition to FMT as the standard of care for C difficile colitis. Capsules may indeed be less distasteful to patients than fecal enema, NG tube fecal instillation, or colonoscopic administration. Still, the medical office will have to secure a safe donor for the recipient (usually an intimate contact or other family member), collect their stool, and process it with a high degree of care and attention (and some specialized equipment). Dr Louie notes that he himself completes the task in his own office-he doesn’t delegate it to nursing or laboratory personnel. So, what’s involved?

In this study, inclusion criteria were more than 3 rCDI episodes and availability of a related donor who passes screening for blood-borne disease and enteric pathogens. Before the procedure, patients were controlled with oral vancomycin. On the day of the procedure, the donor provides a 100-g sample of freshly passed feces, which is suspended in buffered saline and undergoes nearly 3 hours of serial centrifugation and decantation. The resulting pellet is re-suspended with minimal saline and micropipetted into multi-layered gelatin capsules. Typically the patient ingests several dozen capsules (adjusted for body size) over a short time, on an empty stomach. Dr Louie notes that the finished capsules are effectively odorless and are well tolerated. In vitro testing showed that the capsules are likely to remain intact for 1 to 2 hours in vivo-they probably avoid stomach acid deactivation by releasing their bacterial load in the distal small intestine.

Since 2010, 26 of 27 subjects undergoing the methodology experienced permanent C difficile cure, demonstrated by symptom resolution and repeated C difficile–negative stool testing. The one patient who experienced recurrence did so after an antibiotic course. The detailed methodology has not yet been published, making this difficult to reproduce widely (apparently publication is forthcoming).

There are other barriers to wider implementation of this novel and effective approach, which insulates the patient (but not the medical office) from the more unpleasant aspects of FMT. It is non-reimbursable, and there is no billing code for the methodology, making it an investigational therapy at the moment. Dr Louie notes that there is currently no commercial development but notes that he is “hopeful” that this may change. Much will hinge on future research that may identify which bacteria are the key ones to re-establish normal colonic flora; pure cultures may someday replace whole-stool extracts like Dr Louie’s.


Source
Louie T, Cannon K, O’Grady H, et al. Fecal microbiome transplantation (FMT) via oral fecal microbial capsules for recurrent Clostridium difficile infection (rCDI). Paper presented at: IDWeek 2013; October 3, 2013; San Francisco.