Extended-Interval Dosing of Rezafungin against Azole-Resistant Aspergillus fumigatus

Antimicrob Agents Chemother. 2019 Sep 23;63(10):e01165-19. doi: 10.1128/AAC.01165-19. Print 2019 Oct.

Abstract

We evaluated extended-interval dosing of the investigational echinocandin rezafungin (1, 4, and 16 mg/kg on days 1, 4, and 7 postinoculation) for the treatment of disseminated invasive aspergillosis caused by azole-resistant Aspergillus fumigatus Survival was significantly improved in mice treated with each dose of rezafungin and supratherapeutic posaconazole (20 mg/kg twice daily). Kidney fungal burden, as measured by quantitative real-time PCR, was also significantly reduced in mice treated with rezafungin although variability was observed.

Keywords: Aspergillus fumigatus; TR34/L98H; azole resistance; invasive aspergillosis; murine model; rezafungin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / pathogenicity*
  • Azoles / adverse effects
  • Azoles / therapeutic use*
  • Drug Resistance, Fungal / genetics
  • Echinocandins / adverse effects
  • Echinocandins / therapeutic use*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Kidney / virology
  • Male
  • Mice
  • Real-Time Polymerase Chain Reaction
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Azoles
  • Echinocandins
  • Fungal Proteins
  • Triazoles
  • posaconazole
  • Rezafungin