Where: St. Luke's Health Care System in Duluth, Minn.
The issue: Curing recurrent Clostridium difficile infections without fecal transplantation.
By the time C. difficile patients get to Johan S. Bakken, MD, FACP, an infectious disease specialist and clinical associate professor at the University of Minnesota, they have already tried almost everything.
“Most of the patients that had been referred to me had been given customary probiotic agents,” said Dr. Bakken. They had also tried the usual antibiotics, metronidazole or vancomycin. After those treatments failed and the patients suffered with diarrhea, for years in some cases, they came to Dr. Bakken for the last resort—fecal microbiota transplantation.
But transplantation wasn't possible for some patients. “For various reasons, [patients] elected not to pursue that form of treatment, either because they couldn't afford it, that is, the cost of screening the donor of the fecal sample; or they had adverse opinions about fecal transplantation; or they simply couldn't locate a donor of stool,” said Dr. Bakken.
This led him to contemplate alternative treatments for recurrent C. difficile. “It dawned on me why all these treatments had failed had to do with the fact that none of the programs dealt with the spores that were left in the colon,” said Dr. Bakken. “When [C. difficile] convert to a spore-form stage, then the antibiotic agents have no impact on their survival. It seemed that one would need to think along the lines of a bacterium.”
How it works
To trick the bacteria, Dr. Bakken came up with a staggered, tapered antibiotic withdrawal regimen. Once a patient was diarrhea-free on a typical anti-C. diff antibiotic regimen, the doses would be stretched to 72-hour intervals with a reduction in dose every 2 weeks, for a total of 6 weeks. “My theory was that over time, you would basically deplete the spore reservoirs so that there would be very, very few actively growing C. diff organisms in the colon,” Dr. Bakken said.
To further confound the organisms, his patients drank kefir, a fermented milk product containing 10 to 12 probiotic agents, with every meal. “The probiotic agents may occupy binding sites that C. diff also needs to occupy and they may compete for food sources. They may have positive beneficial interactions in the immune system on the epithelial lining, in the intestinal tract. They may even promote substances that are injurious or noxious to C. diff,” he said.
From 2009 to 2012, Dr. Bakken tried the regimen on 8 patients, all of whom were cured. Based on that success, he treated 18 more. “I kind of made it into a habit of offering either fecal transplantation or the taper program,” he said.
One patient didn't comply and dropped out. Of the other 17, all but 4 were diarrhea-free at 9 months. Those 4 were successfully treated with 2 weeks of vancomycin followed by 2 weeks of rifaximin. The results suggest that the combination of the antibiotic withdrawal and the kefir could be as effective a treatment for recurrent C. difficile as fecal transplant, Dr. Bakken concluded when he published his results in the June 27 Clinical Infectious Diseases.
The cost of the regimen—kefir drinks and about 100 vancomycin tablets—is likely less than the screening and procedure expenses of fecal transplantation, and the risk of adverse effects appears to be low, according to Dr. Bakken. “The biggest risk is that it doesn't work. I'm not aware of any risks with the intake of kefir ... It's an over-the-counter agent that can be purchased virtually everywhere,” he said.
“Ideally, we should have a randomized protocol, a prospective clinical trial, that compares this type of treatment to standard treatment, a gradual taper, or perhaps even fecal transplantation,” said Dr. Bakken.
However, such a trial would require significant funding, so the evidence is likely to remain anecdotal for a while. “I've discussed this treatment approach with colleagues who also adopted this, and the feedback I've gotten has been that it has worked. I don't know how many patients have been subjected to this treatment, but I haven't had any feedback that says that this doesn't work,” said Dr. Bakken.
Dr. Bakken hopes to get more feedback if the publication of his treatment regimen encourages other clinicians to test it out. Patients, at least, appear to be ready. “I've received correspondence from potential patients that have gone online and found [my study],” he said. “I hope this provides an alternative to a very difficult and prevalent problem.”