Effects of Echinocandins in Combination with Nikkomycin Z against Invasive Candida albicans Bloodstream Isolates and the fks Mutants

Antimicrob Agents Chemother. 2017 Oct 24;61(11):e00619-17. doi: 10.1128/AAC.00619-17. Print 2017 Nov.

Abstract

We evaluated the in vitro and in vivo effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two Candida albicans isolates and their lab-derived echinocandin-resistant fks mutants with FKS1 S645Y and FKS1 S645P. Synergistic effects were observed in all tested strains (fractional inhibitory concentration index, <0.5). Enhanced survival was observed in an immunocompromised murine model (log-rank test, P < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance.

Keywords: Candida albicans; FKS; echinocandin; nikkomycin Z.

MeSH terms

  • Aminoglycosides / pharmacology*
  • Anidulafungin
  • Animals
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / genetics
  • Candida albicans / isolation & purification
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Chitin Synthase / antagonists & inhibitors
  • Drug Combinations
  • Drug Resistance, Fungal / genetics
  • Drug Synergism
  • Echinocandins / pharmacology*
  • Glucosyltransferases / genetics
  • Humans
  • Lipopeptides / pharmacology*
  • Micafungin
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests

Substances

  • Aminoglycosides
  • Antifungal Agents
  • Drug Combinations
  • Echinocandins
  • Lipopeptides
  • Anidulafungin
  • nikkomycin
  • Glucosyltransferases
  • Chitin Synthase
  • Micafungin

Supplementary concepts

  • Systemic candidiasis