Determination of pharmacodynamic target exposures for rezafungin against candida tropicalis and candida dubliniensis in the neutropenic mouse disseminated candidiasis model

Abstract

Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4 Candida tropicalis and 4 Candida dubliniensis strains, using the neutropenic mouse invasive candidiasis model. The area under the concentration-time curve (AUC)/MIC was a robust predictor of efficacy (R2 = 0.93 and 0.72, respectively). The stasis free-drug 24-h AUC/MIC target exposure for the group ranged from 3 to 25, whereas the 1-log-kill free-drug 24-h AUC/MIC target exposure ranged from 4.3 to 62. These values are similar to those found in previous rezafungin PD studies with other Candida spp. Based on recent surveillance susceptibility data, AUC/MIC targets are likely to be exceeded for >99% of C. tropicalis and C. dubliniensis isolates with the previously studied human dose of 400 mg i.v. once weekly.