| Summary: | <i>Candida auris</i> is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences the killing activities of echinocandins against <i>C. auris</i> is currently lacking. We determined the killing activities of anidulafungin and micafungin (0.25, 1, 8, 16 and 32 mg/L each) with and without nikkomycin Z (8 mg/L) against 15 isolates representing four <i>C. auris</i> clades (South Asian n = 5; East Asian n = 3; South African n = 3; South American n = 4, two of which were of environmental origin). Two and one isolates from the South Asian clade harbored mutations in the hot-spot 1 (S639Y and S639P) and 2 (R1354H) regions of the <i>FKS1</i> gene, respectively. The anidulafungin, micafungin and nikkomycin Z MIC ranges were 0.015-4, 0.03-4 and 2->16 mg/L, respectively. Anidulafungin and micafungin alone exerted weak fungistatic activity against wild-type isolates and the isolate with a mutation in the hot-spot 2 region of <i>FKS1</i> but was ineffective against the isolates with a mutation in the hot-spot 1 region. The nikkomycin Z killing curves were always similar to their respective controls. Twenty-two of sixty (36.7%) anidulafungin plus nikkomycin Z and twenty-four of sixty (40%) micafungin plus nikkomycin Z combinations produced at least 100-fold decreases in the CFUs (synergy), with a 41.7% and 20% fungicidal effect, respectively, against wild-type isolates. Antagonism was never observed. Similar results were found with the isolate with a mutation in hot-spot 2 of <i>FKS1</i>, but the combinations were ineffective against the two isolates with prominent mutations in hot-spot 1 of <i>FKS1</i>. The simultaneous inhibition of β-1,3 glucan and chitin synthases in wild-type <i>C. auris</i> isolates produced significantly greater killing rates than either drug alone. Further studies are warranted to verify the clinical efficacy of echinocandin plus nikkomycin Z combinations against echinocandin susceptible <i>C. auris</i> isolates.
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