Fidaxomicin shows improved efficacy in treating pediatric C. difficile

SAN FRANCISCO — Treatment with fidaxomicin led to higher overall cure rates among children who were infected with Clostridoides difficile compared with treatment with vancomycin, according to research presented at IDWeek.

“The antibiotic-associated Clostridoides (formerly Clostridium) difficile infection (CDI) can a cause severe illness, prolonged hospitalization, and even contribute to risk of mortality in both children and adults,” Joshua Wolf, MBBS, assistant member of the infectious diseases department at St. Jude Children’s Research Hospital, told Infectious Diseases in Children. “Treatment with standard therapy of vancomycin or metronidazole is usually successful initially, but recurrence of infection is very common, especially if additional antibiotic courses are required. Although fidaxomicin, a novel macrocyclic antibiotic, is known to be associated with superior outcomes for treatment of CDI, mostly by reducing recurrent infection, little was known about the safety and efficacy of this drug in children.”

Fidaxomicin is marketed in the United States as Dificid (Merck). It was approved by the FDA in 2011 for the treatment of C. difficile-associated diarrhea in adults. It has not been approved as treatment in children.

Wolf and colleagues conducted the phase 3 SUNSHINE study, which compared fidaxomicin with vancomycin for the treatment of CDI in children. The researchers randomly assigned patients aged younger than 18 years with newly confirmed CDI and diarrhea in a 2:1 fashion to receive 10 days of treatment of either fidaxomicin, a narrow-spectrum macrocyclic antibiotic, in an oral suspension of 32 mg/kg per day or tablet form of 200 mg twice a day, or vancomycin in an oral liquid of 40 mg/kg per day or capsule of 125 mg four times a day. Using other antibiotics concurrently was not permitted in the study. The researchers used confirmed clinical response (CCR) at day 12 — defined as no diarrhea for 2 consecutive days while receiving treatment and remaining well until treatment was discontinued — as the primary endpoint.

The researchers conducted an analysis of 142 patients, including 98 in the fidaxomicin cohort and 44 in the vancomycin cohort. They divided patients by age, including patients aged younger than 2 years (n = 30), aged 2 to younger than 6 years (n = 48), aged 6 to younger than 12 years (n = 36) and aged 12 to younger than 18 years (n = 28).

Wolf and colleagues reported that 28.6% of patients in the fidaxomicin cohort and 22.7% in the vancomycin cohort had prior CDI at baseline. There were 75.3% of patients in the fidaxomicin cohort and 57% of patients in the vancomycin cohort who experienced at least one treatment-emergent adverse event. Three patients in the fidaxomicin cohort and two patients in the vancomycin cohort died after the 40-day study period ended; however, none of the deaths were related to treatment, according to the researchers.

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Patients in the fidaxomicin cohort experienced a trend to improved CCR and other efficacy outcomes, which the researchers reported was statistically significant for global cure (adjusted difference = 18.8%; 95% CI, 1.5%-35.3%).

“The study found that safety and initial efficacy were similar for both treatments, but overall cure of infection (comprising good initial response plus lack of recurrence during the 40-day study period) was more common in participants receiving fidaxomicin,” Wolf said. “According to this study, only five patients would need to be treated with fidaxomicin to prevent one additional episode of treatment failure. This suggests that fidaxomicin is a reasonable choice for treatment of pediatric CDI.” – by Bruce Thiel

Reference:

Wolf J, et al. Abstract LB12. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.

Disclosures: Wolf reports serving as a consultant for Astellas, which sponsored the study, and receiving medical writing support from Cello Health MedErgy, which was funded by Astellas. Please see the study for all other authors’ relevant financial disclosures.