Clostridioides difficile infection (CDI), formerly known as Clostridium difficile infection, is increasingly recognized as a public health threat beyond its prevalence as a cause of diarrheal illness in hospitalized adults. In data from a 2011 CDC-funded study, CDI reportedly led to 453 million infections and about 29,000 deaths in the United States alone. Forty-one percent of these cases were community acquired.
Beyond treatment with antibiotics, fecal microbiota transplantation (FMT) is commonly used to treat CDI, but the effects of FMT had not been well-studied in children. Earlier this year, in a retrospective study of pediatric and young adult patients at 18 centers published in Clinical Gastroenterology and Hepatology, investigators found that FMT is effective and safe for the treatment of CDI.
Challenge of Recurrent Infections
“One of the unique challenges associated with C. diff is that it often recurs,” said Maribeth Nicholson, M.D., assistant professor of pediatrics at Vanderbilt University Medical Center and first author on the pediatric study. “After an initial infection, approximately 20 to 30 percent of pediatric patients have a recurrence of disease. After two episodes of infection, the rate of recurrence is closer to 50 percent.”
There are multiple reasons for recurrence, including persistent dysbiosis of the microbiome, continued CDI exposures, and an inadequate immune response. “C. diff usually responds well to antibiotics, but when you pluck out important community members from the microbiome, the system is predisposed to recurrent infections,” Nicholson said. “These spores are now everywhere in the environment. By transplanting the microbiota from a healthy host, you’re preventing C. diff from reestablishing itself.”
FMT Effectiveness in Children
The multicenter study reviewed FMT for the treatment of CDI in 335 children and young adults, with no episodes of recurrent CDI (rCDI) in 81 percent of the patients. In the 64 patients that experienced CDI recurrence, 34 (53 percent) underwent repeat FMT, which was successful in 19 patients (56 percent). Overall, success rate of one or two FMTs in the treatment of rCDI was 87 percent. This is similar to success rates reported in adults.
Factors associated with a successful FMT included the lack of a feeding tube, the use of fresh stool versus thawed and previously frozen stool, delivery via colonoscopy, and fewer CDI episodes before undergoing FMT. “Future studies of FMT are needed to fully evaluate the efﬁcacy, safety, optimal timing, dose, delivery route and preparation of FMT in children with CDI,” Nicholson said.
“These spores are now everywhere in the environment. By transplanting the microbiota from a healthy host, you’re preventing C. diff from reestablishing itself.”
Improving FMT Delivery
Currently, FMT is not FDA approved and can only be used in rCDI. And recently, the FDA issued a safety alert when two immunocompromised adults had multi-drug resistant infections that linked back to their FMT. “There’s been some thought recently that there must be a better, more standardized way to do this,” Nicholson said. “Do we really need to give full feces to correct this dysbiosis?”
Several companies have engineered products with specific bacterial components that can be administered in pill form. “Some have had some success, but some haven’t,” Nicholson said, “which makes us think that it’s not just the bacteria in the sample, but other components that affect the efficacy as well.” Investigators from Vanderbilt’s Vaccine and Treatment Evaluation Unit are participating in a randomized, placebo-controlled study of adults with CDI to evaluate the safety and efficacy of FMT delivered by enema.
Because many chronic illnesses are thought to be affected by some level of gut dysbiosis – not only gastrointestinal conditions but depression, autism, food allergies and others – there are currently numerous studies testing FMT for various indications. Nicholson hopes it will be approved for treatment beyond rCDI in the future, with better efficacy and safety data.
“Patients really suffer with C. diff; they’re desperate for relief,” Nicholson said. “Despite the lack of FDA approval, I’ve yet to have someone say, ‘I wouldn’t want to do that’ when presented with FMT as an option. They feel so much better immediately following the procedure.”