Fidaxomicin for the Treatment of Clostridium Difficile Infection in the Pediatric Population - Not Quite So Soon Yet

Abstract

Fidaxomicin is a new narrow spectrum macrocyclic antibiotic. It inhibits bacterial RNA polymerase and eradicates C difficile with minimal effect on normal intestinal flora. The US FDA granted orphan drug designation for all formulations of fidaxomicin for the treatment of C difficile infections in pediatric patients on January 10, 2011. Fidaxomicin has bactericidal activity against C difficile with a prolonged post-antibiotic effect. Even though this medication has an orphan designation for pediatrics, all the available pharmacokinetic and pharmacodynamic data were in subjects >= 18 years old. The MIC₉₀ for fidaxomicin against C. difficile varies from 0.0078 to 0.25 mcg/ml. Fidaxomicin is poorly absorbed. The highest peak plasma concentration in patients treated with fidaxomicin was 0.191 mcg/ml. Fecal levels of fidaxomicin after oral administration are extremely high. The average fecal concentrations in C difficile patients were 255.6 mcg/g, 441.7 mcg/g, and 1443.3 mcg/g in the 100, 200, and 400 mg/day groups, respectively. At a dose of 400 mg/day the average fecal concentration was 5700 times higher than the highest MIC₉₀ of fidaxomicin against C difficile. In a phase III clinical trial fidaxomicin 200 mg twice daily was compared with vancomycin 125 mg four times per day orally for 10 days. Only two patients were 18 years old, and no patients younger than 18 years old participated in the study. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin. Patients who were infected with non-North American Pulsed Field type 1 strains had fewer recurrences in the fidaxomicin group than patients in the vancomycin group. Side effects were similar between both therapies. Most patients experienced mild gastro-intestinal symptoms. Fidaxomicin is a good therapeutic alternative to vancomycin and metronidazole, especially in patients with recurrence of C difficile infection. Patients rarely experience systemic side effects which improves compliance. The dose of fidaxomicin is expected to be 200 mg given orally twice a day for patients 16 years and older. At this point, Optimer Pharmaceuticals Inc has conducted clinical trials in adults only. Additional clinical trials in pediatric patients are needed before therapeutic recommendations can be made in this population.

Gastroenterol Res. 2011;4(3):93-96
doi: https://doi.org/10.4021/gr318e