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

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Summary

Introduction

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].

Results
Conclusion

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