Synergistic anticandidal activity of etomidate and azoles against clinical fluconazole-resistant Candida isolates

Future Microbiol. 2019 Nov:14:1477-1488. doi: 10.2217/fmb-2019-0075. Epub 2020 Jan 9.

Abstract

Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.

Keywords: Candida spp.; azoles; biofilm; etomidate; synergism.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Azoles / pharmacology*
  • Biofilms / drug effects
  • Candida / drug effects*
  • Cell Survival / drug effects
  • Cricetinae
  • DNA Damage / drug effects
  • Drug Discovery
  • Drug Resistance, Fungal*
  • Drug Synergism
  • Etomidate / pharmacology*
  • Fibroblasts / drug effects
  • Fluconazole / pharmacology*
  • Lung / cytology
  • Lung / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Microbial Sensitivity Tests

Substances

  • Antifungal Agents
  • Azoles
  • Fluconazole
  • Etomidate