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Options to treat childhood C. diff. infection studied

Sep. 12, 2013, 8:37 AM

Maribeth Nicholson, M.D., examines Kynslee Allen as her mother, Kristen, looks on. Kynslee is being treated for C. diff. infection, among the most serious causes of diarrhea. (photo by Steve Green)

After more than a month in and out of the hospital with her daughter, Kynslee, Kristen Allen felt she was at the end of her rope. Last spring, the nearly 2-year-old Columbia girl developed diarrhea that wouldn’t go away after taking antibiotics for repeated ear infections.

“She is such a spunky girl, with personality for days. But she would just lay on the floor, lifeless. She wouldn’t eat and she couldn’t keep medicine down. I was worried she might die,” said Allen.

When doctors finally determined Kynslee had an infection called “C. diff.,” Allen said it was the first time she had ever heard of it. The Clostridium difficile bacteria and toxins are among of the most serious causes of diarrhea, and rates of C. diff. colitis have surged in the last decade. It is more common in people who have had recent, extended antibiotic use or hospitalization, including the young and especially the elderly.

Another major risk factor for getting C. diff. colitis is having had the illness before. Kynslee had a second bout just weeks after finally recovering from the first one.

“We know 20 percent of kids will have recurrence, and if it comes back they are at high risk of it coming back again and again. But we know very little about the reasons this happens. That’s why we’re working on our study,” said Maribeth Nicholson, M.D.

Nicholson, a Vanderbilt Gastroenterology, Hepatology, and Nutrition fellow, has begun a research project, funded by a Thrasher Early Career Award program grant, to follow children after their first C. diff. infection and examine recurrence.

“There have been no publications to date on risk factors for recurrence in children. Some have been completed in the adult population, but even those are relatively new,” Nicholson said.
Along with partnering institution Texas Children’s Hospital, Nicholson and her mentor, Kathryn Edwards, M.D., Sarah H. Sell and Cornelius Vanderbilt Professor of Pediatrics and director of the Vanderbilt Vaccine Research Program, hope to enroll 200 children during their first episode of C. diff. colitis. The team will follow the children for 60 days to see which ones suffer a recurrence and then will examine a number of biomarkers that Nicholson says she hopes will illuminate the causes of recurrence.

“For example, a specific genetic polymorphism has already been found in adults, related to overproduction of inflammation in the colon. We plan to examine this in children. We will also look at a particular strain of C. diff. known as NAP1, that has been characterized in the last couple of years, and may be related to recurrent disease,” Nicholson said.

Nicholson says the current treatment for C. Diff. colitis — antibiotics — is less than ideal for a condition caused by antibiotics in the first place. Vanderbilt is currently evaluating the use of a new and extremely effective treatment for recurrent C. diff. colitis: fecal microbiota transplantation. In this treatment, a fecal sample is taken from a parent or spouse or other close relative, and is given to the patient through either a tube into the stomach/small intestine, or at the time of colonoscopy, to restore the balance of bacterial flora in the gut. The treatment is more than 90 percent effective in stopping diarrhea in just a few days or even hours and preventing further episodes of recurrence.

While Kynslee has responded to the antibiotic treatment so far, and has not been offered a fecal transplant, Allen says the thought of this rather unorthodox treatment is far better than the thought of dealing with C. diff. again.

“It was awful for us, awful for her, and I had to take about three months off of work. It has changed my opinion of antibiotics (for common infections) completely. It steers me completely away from antibiotics for everyone in my family,” Allen said.

Kynslee experienced her first infection before the start of Nicholson’s study and is not eligible to participate. But since doctors say the infection could return, Allen said she is glad the work is underway to examine why recurrence happens, and will be watching for the results.

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