Ibrexafungerp prolongs survival and reduces the eumycetoma grain size in Galleria mellonella infection models of two different causative agents of eumycetoma.

Abstract

Objectives: Eumycetoma is a neglected tropical fungal disease of the subcutaneous tissue that is currently not treatable with medication only. Standard itraconazole therapy is combined with surgical excision of the lesion. Recently, ibrexafungerp, a novel oral antifungal agent inhibiting 1,3-β-D-glucan synthesis, was approved by the United States Food and Drug Administration (FDA) for the treatment of vulvovaginal candidiasis. In this study we determined the in vitro activity and in vivo efficacy of ibrexafungerp in eumycetoma causative agents.

Methods: In vitro activity of ibrexafungerp and itraconazole was determined against 30 Madurella and 7 Falciformispora isolates by standardized in vitro susceptibility assays. The in vivo efficacy of ibrexafungerp, itraconazole and the combination of ibrexafungerp and itraconazole was determined by measuring the 10 day survival in M. mycetomatis and F. senegalensis grain models in Galleria mellonella larvae. Grain number and size were determined in Grocott- and haematoxylin and eosin-stained sections.

Results: Ibrexafungerp inhibited the growth of Madurella and Falciformispora species with MICs ranging from 4 to 64 mg/L and from 8 to 32 mg/L, respectively. In G. mellonella larvae, ibrexafungerp was not toxic and prolonged the survival in M. mycetomatis-infected larvae 10 days after infection, but not in F. senegalensis-infected larvae. Combining ibrexafungerp with itraconazole prolonged the survival of M. mycetomatis- and F. senegalensis-infected larvae. Treatment with ibrexafungerp alone and in combination resulted in smaller grains in M. mycetomatis-infected larvae.

Conclusions: Ibrexafungerp showed in vitro activity and in vivo efficacy against the two most common eumycetoma causative agents.