Faecal microbiota transplant (FMT), or the transfer of stool from a healthy donor to a patient, has been found highly effective in reversing severe Clostridiodes difficile diarrhoeal infections in adults. C. difficile disease is known to be associated with an altered intestinal microbiota, and the transplanted stool appears to restore a normal balance.
Is FMT helpful in children with C. difficile? The largest FMT study in children to date, found it both safe and effective and also identifies predictors of success.
Diarrhoeal disease from C. difficile on the rise among children. One population-based study found a 12.5-fold increase in incidence from 1991 to 2009. For reasons that aren't clear, C. difficile is more frequently striking children without such risk factors as hospitalization or antibiotic exposure.
"Our results are quite exciting, given that recurrent C. diff is debilitating and increasing in children, not just those with known risk factors but previously healthy children as well," says gastroenterologist Dr Stacy A Kahn, at Boston Children's Hospital. Kahn led the study with Dr Maribeth Nicholson, at Vanderbilt University Medical Centre and Dr Richard Kellermayer at Texas Children's Hospital.
The team retrospectively studied 372 patients with C. difficile, age 11 months to 23 years, who had FMT at one of 18 paediatric centres across the US. FMT was administered in various ways, including colonoscopy, nasogastric tube, frozen capsules, or enemas.
Two-month outcomes were available for 335 patients. Of these, 81% had no recurrence of C. difficile infection after a single treatment. Some of the remaining patients had a second round of FMT; about half of them saw no C. difficile recurrence, increasing the overall success rate to 87%.
Success was 2.7 times more likely when FMT came in the form of fresh versus previously frozen stool, and 2.4 times more likely when patients received the stool via colonoscopy versus other methods. Patients without a feeding tube (itself considered a risk factor for C. difficile) were twice as likely to respond, and those with one fewer prior C. difficile infection had a 20% greater chance of success. Age did not appear to be factor.
FMT was also more likely to succeed in patients treated more recently, perhaps because of tighter protocols around donor selection and treatment.
"The success rates we found are similar to what is seen in adults, but seem to be associated with fewer complications," says Kahn. "We don't understand why colonoscopic delivery, fresh stool and more recent FMT treatment were associated with higher success rates. These questions provide the foundation for future FMT research in children."
As for safety, 6% of the patients had FMT-related adverse events; most were mild and included diarrhoea, vomiting, and bloating. Of the roughly one-third of patients who also had inflammatory bowel disease, 2.5% had a severe flare of their illness requiring them to be hospitalised. But it wasn't clear that had anything to do with the FMT.
Kahn notes that the study was limited by its retrospective design and relatively short period of follow-up. "We are using the data to help design future prospective, controlled studies," she says. "We also need longitudinal studies to investigate the long-term impact and safety of transplanting the microbiome from one person to another. A lot more questions need to be answered."
The group is also studying FMT for children with other forms of colitis, such inflammatory bowel disease (IBD).
"We want to tap into the therapeutic potential of FMT and begin to understand how we can use and manipulate the microbiome to treat diseases other than C. diff," Kahn says.
Abstract
Background & Aims: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.
Methods: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMTs at 18 pediatric centers, from February 1, 2004 to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.
Results: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.
Conclusion: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.
Authors
Maribeth R Nicholson, Paul D Mitchell, Erin Alexander, Sonia Ballal, Mark Bartlett, Penny Becker, Zev Davidovics, Michael Docktor, Michael Dole, Grace Felix, Jonathan Gisser, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Judith Kelsen, Melissa Kennedy, Sahil Khanna, Elizabeth Knackstedt, McKenzie Leier;, Jeffery Lewis, Ashley Lodarek;, Sonia Michail, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, George H Russell, Namita Singh, Aliza Solomon, David L Suskind, Steven Werlin, Richard Kellermayer, Stacy A Kahn
[link url="https://www.sciencedaily.com/releases/2019/05/190516114609.htm"]Boston Children’s Hospital material[/link]
[link url="https://www.cghjournal.org/article/S1542-3565(19)30427-6/pdf"]Clinical Gastroenterology and Hepatology abstract[/link]