Pharmacodynamic Evaluation of Rezafungin (CD101) against Candida auris in the Neutropenic Mouse Invasive Candidiasis Model

Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01572-18. doi: 10.1128/AAC.01572-18. Print 2018 Nov.

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 auris strains, using the neutropenic mouse invasive candidiasis model. The area under the concentration-time curve (AUC)/MIC was a robust predictor of efficacy (R2 = 0.76). The stasis free-drug 24-h AUC/MIC target exposure for the group was 1.88, whereas the 1-log-kill free-drug 24-h AUC/MIC target exposure was 5.77. These values are very similar to those in previous rezafungin PD studies with other Candida spp. Based on recent surveillance susceptibility data, AUC/MIC targets are likely to be exceeded for >90% of C. auris isolates with the previously studied human dose of 400 mg administered i.v. once weekly.

Keywords: Candida auris; antifungal therapy; pharmacodynamics; rezafungin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Candida / drug effects*
  • Candidiasis / drug therapy*
  • Disease Models, Animal
  • Echinocandins / pharmacology*
  • Mice
  • Microbial Sensitivity Tests / methods

Substances

  • Antifungal Agents
  • Echinocandins
  • Rezafungin