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

Abstract

We evaluated the <i>in vitro</i> and <i>in vivo</i> effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two <i>Candida albicans</i> isolates and their lab-derived echinocandin-resistant <i>fks</i> 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, <i>P</i> < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance.