In vitro combination of antifungal drugs with tacrolimus (FK506) holds promise against clinical Candida species, including Candida auris

Med Mycol. 2023 Jul 6;61(7):myad069. doi: 10.1093/mmy/myad069.

Abstract

In vitro interactions between tacrolimus, a calcineurin inhibitor, and fluconazole, itraconazole, caspofungin, or anidulafungin were evaluated against Candida auris, C. albicans, C. parapsilosis, and C. glabrata (each five strains). Tacrolimus-itraconazole, tacrolimus-caspofungin, and tacrolimus-fluconazole combinations resulted in synergistic interactions against 95%, 90%, and 60% of Candida isolates, respectively. However, tacrolimus-anidulafungin resulted in only a 35% synergistic effect. A combination of tacrolimus and itraconazole was most potent with synergy against 100% of C. auris, C. parapsilosis, and C. glabrata isolates. Of note, no antagonistic interaction was found.

Keywords: Candida auris; FK506; calcineurin; drug interactions; drug resistance; tacrolimus.

MeSH terms

  • Anidulafungin / pharmacology
  • Animals
  • Antifungal Agents* / pharmacology
  • Candida auris
  • Candida glabrata
  • Candida parapsilosis
  • Candida*
  • Caspofungin / pharmacology
  • Echinocandins / pharmacology
  • Fluconazole / pharmacology
  • Itraconazole / pharmacology
  • Microbial Sensitivity Tests / veterinary
  • Tacrolimus / pharmacology

Substances

  • Antifungal Agents
  • Tacrolimus
  • Fluconazole
  • Caspofungin
  • Anidulafungin
  • Itraconazole
  • Echinocandins