PHILADELPHIA – Fidaxomicin, an approved treatment for Clostridium difficile-associated diarrhea in adults, appears safe and effective in children, according to findings from an open-label study.
The overall clinical response rate was 92% in 38 children aged 11 months through 17 years who were treated with 32 mg/kg/day for 10 days. Although 74% of patients had at least one adverse event, most of the events were mild (45%) or moderate (21%) in severity and were the type of events that would be expected in children with moderate to severe underlying illness, Pam Sears, Ph.D. of Cubist Pharmaceuticals, San Diego, reported at an annual scientific meeting on infectious diseases.
CDC/D. Holdeman
Although three quarters of the children with CDAC saw an adverse event, most were mild or moderate.
The children included in this first pediatric study of fidaxomicin had diarrhea and tested positive for C. difficile toxin. Most had relatively complex medical histories; 24% had neoplasms and 79% had gastrointestinal disorders. They received either the commercial tablet formulation of fidaxomicin or an oral suspension.
Plasma concentrations were generally low, with a mean across the strata ranging from 8.87-16.6 ng/mL and metabolite OP-1118 levels that ranged from 27.5-130 ng/mL at 1-2 hours following the first dose. No age-related trends in concentrations were seen.
Fecal concentrations of fidaxomicin averaged 3,230 mcg/g with a trend toward higher concentrations in the youngest age group. This could be because samples from the youngest group were collected from diapers and could have become dehydrated, Dr. Sears explained the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Of the children in the study with a clinical response, 29% experienced a relapse, but all but one of these children had a history of recurrent C. difficile-related diarrhea.
Fidaxomicin is a first-in class narrow spectrum macrocyclic antibiotic drug approved in the United States and several other countries for the treatment of C. difficile-associated diarrhea in adults.
These findings demonstrate that the pharmacokinetic profile in children is similar to that in adults – with low plasma levels and high fecal concentrations, and suggest that clinical response in children is also excellent, Dr. Sears said.
This study was funded by Cubist Pharmaceuticals. Dr. Sears is an employee of Cubist Pharmaceuticals.