Artemisinins, new miconazole potentiators resulting in increased activity against Candida albicans biofilms

Antimicrob Agents Chemother. 2015 Jan;59(1):421-6. doi: 10.1128/AAC.04229-14. Epub 2014 Nov 3.

Abstract

Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albicans biofilm-related infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology*
  • Artemisinins / pharmacology*
  • Artesunate
  • Biofilms / drug effects*
  • Candida albicans / drug effects*
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Caspofungin
  • Drug Synergism
  • Echinocandins / pharmacology
  • Fluconazole / pharmacology
  • Hexachlorophene / pharmacology
  • Lipopeptides
  • Miconazole / pharmacology*
  • Miconazole / therapeutic use
  • Microbial Sensitivity Tests
  • Pyrvinium Compounds / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Antifungal Agents
  • Artemisinins
  • Echinocandins
  • Lipopeptides
  • Pyrvinium Compounds
  • Reactive Oxygen Species
  • Artesunate
  • pyrvinium
  • Miconazole
  • Amphotericin B
  • Fluconazole
  • Caspofungin
  • Hexachlorophene