Preexposure to Isavuconazole Increases the Virulence of Mucorales but Not Aspergillus fumigatus in a Drosophila melanogaster Infection Model

Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01896-18. doi: 10.1128/AAC.01896-18. Print 2019 Feb.

Abstract

Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model. In contrast to A. fumigatus, a hypervirulent phenotype was found in all tested Mucorales upon preexposure to either voriconazole or isavuconazole. These findings may contribute to the explanation of breakthrough mucormycosis in isavuconazole-treated patients.

Keywords: Aspergillus fumigatus; Drosophila melanogaster; Rhizopus arrhizus; isavuconazole.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / pathogenicity*
  • Drosophila melanogaster
  • Female
  • Mucorales / drug effects
  • Mucorales / pathogenicity*
  • Nitriles / pharmacology*
  • Pyridines / pharmacology*
  • Rhizopus / drug effects
  • Rhizopus / pathogenicity
  • Triazoles / pharmacology*
  • Virulence

Substances

  • Antifungal Agents
  • Nitriles
  • Pyridines
  • Triazoles
  • isavuconazole