APX001A in vitro activity against contemporary blood isolates and C. auris determined by the EUCAST reference method [PublishAheadOfPrint]

APX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one with the EUCAST method. We investigated the in vitro activity of APX001A and five comparators against 540 candidaemia and 122 C. auris isolates.

Isolates (17 Candida and 3 yeast species) were identified using CHROMagar, MALDI-TOF and when needed ITS-sequencing. EUCAST E.Def 7.3.1 susceptibility testing included APX001A, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole. Wild-type upper limits (WT-UL) were established following the EUCAST-principles for Epidemiological cut off value setting for APX001A allowing classification as WT or non-WT.

APX001A MIC₅₀ values (mg/L) were: C. albicans, C. dubliniensis and C. tropicalis 0.004-0.008, C. parapsilosis and C. auris 0.016, C. glabrata 0.06 and C. krusei >0.5. APX001A MICs varied against the rare species from C. pelliculosa ≤0.0005 to C. norvegensis >0.5. APX001A was equally or more in vitro active than the comparators against all species except C. krusei and C. norvegensis. Four isolates were APX001A non-WT, all of which were fluconazole resistant. A correlation was observed between APX001A and fluconazole MICs across all species except C. guilliermondii and C. auris, and when comparing high and low fluconazole MIC isolates of C. albicans, C. dubliniensis, C. glabrata, C. tropicalis and C. auris.

APX001A showed promising in vitro activity against most Candida and other yeast species including C. auris when compared to five comparators. WT-ULs were suggested for the common species and a new and un-explained correlation to fluconazole susceptibility was observed.

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