Stacy Kahn, MD, on FMT in Pediatric Clostridium difficile Infection
Fecal microbiota transplantation (FMT) is commonly used to treat adults with Clostridium difficile infection (CDI). However, research on the safety and efficacy of FMT in children is limited.
In a new study, Stacy Kahn, MD, an attending physician at the Inflammatory Bowel Disease Center and director of the FMT and Microbial Therapeutics Program at Boston Children’s Hospital, and colleagues evaluated data on 372 individuals aged 11 months to 23 years with CDI who underwent FMT. Results showed that FMT was a safe and effective for the treatment of children and young adults with CDI.1
Gastroenterology Consultant caught up with Dr Kahn about the research.
Gastroenterology Consultant: What are the current gaps in pediatric gastroenterology research and gaps in our overall knowledge about CDI?
Stacy Kahn: Currently, there are several gaps in pediatric research. First, compared with treatments for adults, it typically takes years for treatments to be studied and approved among children. So, not all of our available treatments for CDI have been studied in children. Second, we do not have a full understanding of the epidemiology of CDI among children. It is difficult to capture the true rate of infection as some patients are treated in the community and others are treated in major hospitals. CDI is also less common among children than among adults. The challenge is that many of the current treatment options are not associated with a full clinical cure. The standard treatment is antibiotics, and we do have a handful of antibiotics which have variable success rates. There has been a high propensity for recurrence, reported in both pediatric and adult populations. With subsequent infection, the risk of recurrence or inability to clear the infection increases. Once antibiotics have failed, subsequent courses of antibiotics can be used, but again it is with diminishing success. Multiple studies and clinical trials among adults have shown FMT to be highly effective in curing or clearing CDI. However, the data in pediatrics is limited to very small case reports or case series. Additional funding is needed to better study pediatric conditions. We truly need to expand and expedite our pediatric research programs so that we can better understand how diseases impact younger patients and in order to develop the safest and most effective treatments for children.
GASTRO CON: What is the biggest challenge in the management of CDI among children?
SK: The biggest challenge with CDI is that many of the current treatment options are not associated with a clinical cure. The standard treatment for CDI is antibiotics. We have a handful of antibiotics available, but the cure rates vary. CDI also has a high propensity for recurrence. With subsequent infection, the risk of recurrence increases. Once antibiotics have failed, subsequent courses of antibiotics can be used, but it is with diminishing success. We need newer treatments to target those at risk of recurrent CDI, and we need to find treatment options to prevent recurrence in the first place. Another significant challenge is that the use of antibiotics to treat CDI is not without potential consequences. While antibiotics are used to kill harmful bacteria, they can also kill the healthy bacteria in the gut, leading to an imbalance of the healthy and harmful intestinal bacteria. Further, after an infection or antibiotic use, it can take weeks to months for the bacterial communities to get back to a baseline. We have to remember that every time we wipe away the healthy bacteria, we are potentially exposed to risk of other infections or conditions. We know that antibiotics are absolutely necessary in the setting of a serious bacterial infection, but we also need to recognize that the unnecessary use of antibiotics occurs and may have a long-term impact on our health.
GASTRO CON: What is the most important finding from the study?
SK: We demonstrated that CDI, when managed with FMT, has an 80% to 87% cure rate in children. We were able to examine a very large group of children from a wide variety of centers across the United States. It included over 370 children with recurrent CDI from urban and rural settings as well as academic centers and pediatric practices. These cure rates are similar to findings from studies with adults. The findings of our study serve as an important first step in describing the safety and efficacy of FMT among children with recurrent CDI. Many more studies are needed to understand the best way to perform and deliver FMT, as well as which patients are appropriate for the treatment. We also reaffirmed that the microbiome is an important therapeutic target not just for adults, but for children. More research is needed to understand how we interact with our microbiome and the ways in which we can capitalize on the microbiome as a potential therapy is crucial, not just for CDI, but for other conditions as well.
GASTRO CON: What is the ideal timing of FMT for children with CDI?
SK: The optimal timing of FMT is something we are still learning about. Currently, we can use FMT to treat patients who have had 3 or more CDI infections or 2 or more infections if the presentation is more severe. The timing of FMT is tricky because we do not want to treat people with colonized CDI and have a false positive on the CDI tests or those with another cause for their symptoms. The key is to identify patients who have CDI that is recurrent and/or are not responding to standard medical therapy. As research in this area expands, we hope to be able to better identify the most appropriate patients, timing, and FMT delivery protocols.
GASTRO CON: Can we predict which children with CDI will undergo successful FMT?
SK: More research is needed to answer this question. Our study was conducted with a retrospective cohort and to truly answer this question we need to conduct prospective randomized controlled trials. We found a few risk factors were associated with FMT success in our study. We found that children who received FMT with fresh donor stool, underwent FMT via colonoscopy, did not have a feeding tube, or had 1 less episode of CDI before FMT had a higher likelihood of successful FMT. Additional studies are needed to understand the differences between those who received fresh donor stool and those who did not. Feeding tubes, both in adults and children, are a risk factor of CDI and recurrent CDI so it is not surprising that children without feeding tubes fare better following FMT. We have also recently published the first international guidance on FMT for CDI among children which is a useful resource for those who want to learn more.
Reference:
- Nicholson MR, Mitchell PD, Alexander E, et al. Efficacy of fecal microbiota transplantation for Clostridium difficile infection in children. Clin Gastroenterol Hepatol. 2019;pii:S1542-3565(19)30427-6. doi:10.1016/j.cgh.2019.04.037.