C diff Infection in Children
Why should children with recurrent disease have to suffer four bouts of infection before recurrence-preventing therapy is administered?
For the past two years I have served on the Board of Directors of the Peggy Lillis Foundation (PLF). PLF strives to increase awareness of Clostridioides difficile disease through education for patients and providers and to influence policy on prevention and therapy of this serious disease.
This disease upsets lives and strains families, especially when severe or recurrent. To understand just how horrible this disease can be, all you have to do is look at the PLF website and read some of the stories by survivors and by families of those who did not survive. PLF was established to honor the memory of Peggy Lillis, who died of a community-acquiredC. diff infection at the young age of 56 years and to provide a legacy of public service in her memory.
Although C. diff is treatable and patients usually respond to antibiotics for their initial infection, severe disease and recurrence post-therapy remain intractable problems. Recurrence occurs in about 20-30% of cases. The risk of recurrence is elevated in the elderly and in those with underlying conditions. Therapies are available to help prevent recurrent disease – but access to these efficacious treatments is limited. I have discussed this in a previous blog. But today, I want to delve into a particularly poignant and frustrating problem – that of serious and recurrent C diff in children.
Fidaxomicin is an antibiotic used to treat C. diff infections and help prevent recurrence. It is now recommended as a front-line treatment for infection, especially for those at high risk of recurrence or who have experienced their first recurrence. But, its expensive compared to other antibiotics, around $3,000-$4,000 per course of therapy. It is approved for use in children, but it is rarely used. Why? Are providers not aware of its approval? Are payers unwilling to cover its cost? I don’t understand, as preventing a significant percentage of recurrences would likely make it more cost-effective than other “cheaper” therapies.
Even in Europe, where efficacious C diff treatment is much more widely available than in the US, fidaxomicin is reserved for children at the third recurrence. The latest Hopkins practice guidelines reiterate this approach. The American Academy of Pediatrics is vague on recommendations for recurrent disease in children and cautions against FMT because of possible contamination of donor stool with unscreened pathogens and limited experience in children. Current screening protocols should very significantly reduce the risk of transmission of pathogens by FMT.
In the US, the situation is even worse. There are now only two approved biological therapies approved to prevent further recurrence in adults, generally given only at the second recurrence – Vowst (oral capsules) ($17,500 without insurance) and Rebyota (delivered via colonoscopy) ($9,999). Neither is approved for pediatric use, and neither has ongoing trials to seek such approval as far as I am aware. Therefore, they are used off-label for children and are generally not covered by insurance.
Our old standby before these two products were approved by FDA was fecal microbial transplant (FMT) using donor-derived material. This was very efficacious, had a price tag of something like $1500, and could be used in children with severe or recurrent disease. That is still the case in Europe (though they must wait until the third recurrence). In the US, because of FDA regulatory changes in the past several years, FMT is only available at limited treatment centers under an investigational protocol. I’m not sure what the cost is currently. PLF is aware of several children in the US suffering through multiple recurrences due to a lack of access to recurrence-preventing therapy.
Why should these children have to suffer through four bouts of this disease? Why should their risk of serious complications be elevated in this way? Perhaps things will improve in this regard now that fidaxomicin has become generic (generic tablets are available but not liquid forms for children) or when newer, less costly therapies to prevent recurrence enter the market.
I believe that the current practice of waiting until the third recurrence of C. difficile infection (therefore the fourth episode of disease) in children before providing therapy with agents that prevent further recurrence is unnecessary, not cost effective and perhaps even cruel. I am hopeful that in the US the FDA will come back to a common-sense regulation of fecal microbial transplantation for adults as well as children. I am also hoping that we see Europe become less restrictive on the use of recurrence-preventing therapies for children in the near future.