C difficile infection generally occurs after patients take antibiotics, wiping out the “good” bacteria in the gastrointestinal system, allowing the pathogen to flourish and produce severe diarrhea. Since C difficile was initially identified as a cause of antibiotic-associated diarrhea in the 1970s, the incidence of C difficile infections has increased and infections have become more severe as highly toxigenic strains have emerged.
Each year, C difficile sickens half a million Americans and contributes to 14 000 deaths; infections result in more than $1 billion in excess health care costs, according to the Centers for Disease Control and Prevention (CDC). The CDC named C difficile infection 1 of the 3 most urgent threats in a recent report.
Most C difficile infections resolve after treatment with either metronidazole or oral vancomycin. However, in some cases, infection recurs despite standard treatment, with a small proportion of patients experiencing multiple relapses. In such cases, physicians have sometimes attempted to halt this cycle of recurrent C difficile by transplanting feces from healthy donors into the affected individual’s gastrointestinal system (fecal microbiota transplantation) to restore good bacteria in the gut.
Although delivering the stool used in fecal transplantation via enema, colonoscopy, or tube through the nose is highly effective, acceptance has been slow due in part to the logistics of stool preparation as well as what is sometimes called the “yuck factor.”
“Many people might find the idea of fecal transplantation off-putting, but those with recurrent infection are thankful to have a treatment that works,” said Thomas Louie, MD, professor of medicine at the University of Calgary, Alberta, Canada, and the study’s lead author. “Recurrent C difficile infection is such a miserable experience and patients are so distraught that many ask for fecal transplantation because they’ve heard of its success.”
Louie said he first made pills for fecal transplantation when a patient failed to respond to the enema method on 2 occasions and also could not tolerate a nasal tube because of the presence of enlarged veins in the esophagus. To make the pills, the research team processed the donor feces until only bacteria remained. They then encapsulated the bacterial concentrate inside 3 layers of gelatin capsule, a process that takes about 3 hours. This method ensured the pills wouldn’t leak or disintegrate until they were past the stomach and into the small intestine, allowing coverage of more of the gastrointestinal tract than other methods, which are also invasive, more costly, and less comfortable for patients, Louie said.
Study patients ingested between 24 and 34 capsules containing fecal bacteria, usually donated by family members. Even though all patients previously had at least 4 bouts of the infection, researchers reported a nearly 100% success rate. Of 32 patients who have been treated so far, only 1 has experienced a recurrence of C difficile—and that recurrence was mild and occurred in the setting of repeated antibiotic use, Louie said.
“The pills are a one-shot deal and seem to work. They are easier for patients and are well-tolerated,” said Louie. However, issues surrounding scalability of pill manufacturing remain unclear.
A better understanding of which bacteria are the “kingpins” of the fecal microbiota—the ones most critical to restoring balance in the gut—is needed to further refine treatment of C difficile infections, said Louie. He speculated that it may be possible one day to grow these bacteria and produce pills containing the most effective combinations, the “true probiotics” of the future.
“It’s an exciting development in the field and could possibly even be used to maintain the balance of bacteria in the [gastrointestinal] system in patients at risk for C difficile,” he said.