Abstract
ABSTRACTWe 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.
Highlights
Echinocandins are considered first-line treatment for invasive Candida infections [1]
We evaluated the in vitro effects of nikkomycin Z combined with an echinocandin against two Candida albicans isolates (ATCC 90028 and blood culture isolate CA 46503) and their lab-derived echinocandinresistant fks mutants
Treatment with either anidulafungin or micafungin improved the survival of mice infected with the parent strain but not in those infected with the fks mutants
Summary
Echinocandins are considered first-line treatment for invasive Candida infections [1]. KEYWORDS Candida albicans, FKS, echinocandin, nikkomycin Z Treatment failures associated with resistant isolates harboring fks hot-spot mutations have been reported [2, 3]. In vitro synergistic effects were reported when nikkomycin Z was combined with echinocandins against Candida isolates [5, 6].
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