Fecal transplants dramatically improve C. difficile in kids
According to a 2013 Mayo Clinic study, published in Clinical Infectious Diseases, the number of cases of Clostridium difficile infection (CDI or C. difficile) in children increased more than twelvefold over the past two decades. The greatest rise was seen in community-onset infections, which grew from 2.2 per 100,000 persons in 1991 to 23.4 per 100,000 persons in 2009.
During the same period, the disease became more severe and more likely to recur. Current data show that 25 percent of C. difficile infections are recurrent, with the risk of recurrence as high as 60 percent after multiple infections.
These factors, coupled with reduced effectiveness of standard therapeutic agents, have led to a need for new and better treatments, says Mark G. Bartlett, M.D., a pediatric gastroenterologist at Mayo Clinic in Rochester, Minn.
"The classic case of a child whose gut flora has been wiped out by a lot of antibiotics is changing," he notes. "We not only have kids with solid organ transplants, immunodeficiency problems, or chronic sinus and ear infections, but also those who acquire CDI from a family member or day care. What's more, the approved medications — vancomycin and metronidazole — are nowhere near 100 percent effective."
Fecal microbiota transplant program
To address these issues, Dr. Bartlett initiated a fecal microbiota transplant program for young patients with refractory C. difficile infection in April 2013. Fecal transplants, which aim to restore a normal gut microbiome, have an overall cure rate of more than 90 percent. "At that time, just a few places were doing fecal transplants in children, but we felt we were ready. Mayo Clinic in Arizona has had an adult program for several years with a 100 percent cure rate, and we have a successful adult program here that paved the way for us," he says.
Initially, requirements for fecal transplantation were stringent: Patients had to be symptomatic and have failed three rounds of antibiotics. Results have been so positive, however, that there is discussion of using transplants earlier in the disease process. "We have transplanted over 20 children and have had no poor outcomes in the initial cohort or the adult group," he says. "What holds us back from doing more are the sedation required for colonoscopy and the cost of donor screening. In the next wave of patients, we will be looking at cost-effectiveness as part of a nationwide project."
Fecal transplantation can be performed via nasogastric (NG) tube, nasojejunal tube, upper tract endoscopy, colonoscopy and retention enema. Dr. Bartlett prefers colonoscopic infusion because it safely and effectively delivers healthy bacteria to the site of most C. difficile infections and because it seems better for children, who could potentially aspirate stool with NG tubes.
To date, the pediatric program has performed 27 microbiota transplants on 22 patients, with a 100 percent overall cure rate. Although the results haven't been formally analyzed, many patients experienced instantaneous improvement, with formed stools immediately after the procedure. In others, symptoms improved between day four and day seven. "Some parents tell us it's too fast to be true," Dr. Bartlett says.
The program's success has created a therapeutic conundrum, however. "People are approaching us for help with disorders such as inflammatory bowel disease for which we don't have a protocol. In a study that appeared in the Journal of Pediatric Gastroenterology and Nutrition, Michigan researchers proved the safety and feasibility of fecal microbiota transplantation for children with ulcerative colitis.
"But with ongoing inflammatory conditions, you have to do the transplant more frequently for more-modest results. There is also tremendous interest in fecal microbiota transplantation for obesity, about which we're excited but wary. We are also interested in treating abdominal symptoms in kids with autism. We have proved that this is safe for CDI, and even though we've only been doing it a year, we feel we have the logistics down very well."
Dr. Bartlett points out that although parents may be desperate to have their children treated, some in the pediatric medical community remain skeptical. "We have parents whose pediatrician told them fecal microbiota transplantation is dangerous," he says. "So it's important that physicians are aware of our results. They may be less wary if two or three major centers are performing transplants safely and effectively."
Another matter is patient age. Dr. Bartlett has performed fecal transplants on children as young as 1 or 2 years old, because "the parents were so persuasive." Like older children and teens, the younger children showed remarkable improvement. But he notes, "It is more complicated in very young kids with diarrhea because their symptoms may be due to lactose intolerance or another infection. A child's intestinal tract is more likely to be colonized with C. difficile than an adult's is, so just because you see the toxin doesn't necessarily mean it's the problem."
There is also the matter of donors, who at this point must be related to the recipient. Dr. Bartlett tells the story of one East Coast family who traveled to Mayo only to learn that neither parent was a suitable donor. "The next frontier is to have universal donors and freeze-dried stool that we can access without screening every time. I'm hoping that will be the next step," he says.
For more information
Khanna S, et al. The epidemiology of Clostridium difficile infection in children: A population-based study. Clinical Infectious Diseases. 2013;56:1401.
Kunde S, et al. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. Journal of Pediatric Gastroenterology and Nutrition. 2013;56:597.
April 02, 2014