Effects of echinocandins in combination with nikkomycin Z against invasive candida albicans bloodstream isolates and the fks mutants

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 immuno-compromised murine model (log-rank test, P 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance.