VANCOUVER, B.C. – A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.
In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient’s resistance to colonization by C. difficile.
To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).
"Why do it? Because it works," Dr. Johan Bakken, an infectious disease specialist at St. Luke’s Hospital in Duluth, Minn., said at the annual meeting of the Infectious Diseases Society of America.
"It’s a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It’s safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours," he said.
Among the severely ill, he said, "I have not encountered any patients who have not welcomed it."
In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).
A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).
Dr. Bakken made his comments during a debate about fecal transplantation’s merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.
Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.
Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.
"This is 2010, not 1910. We can do better than fecal transplantation," Dr. Gerding said.
Even so, there is "no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials," he said.
"The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff," Dr. Gerding said.
Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.
Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.
It’s less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.
A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.
About 25-30 g of stool are collected from the donor as close to the time of instillation as possible (within 24 hours). The stool is then blended into a slurry with saline or milk.
"You need to dedicate a blender" for the procedure, Dr. Bakken noted.
Next, the stool slurry is passed through a coffee filter or gauze to remove particulate matter.
Nasogastric tube tip placement in the proximal duodenum is confirmed by x-ray; then about 25 mL of the slurry are delivered via syringe.
Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis.
Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.
As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients.
"Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse," Dr. Bakken joked.
Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.