A multicentre study for determination of epidemiological cut-off values for Candida auris with EUCAST broth microdilution reference methodology

BACKGROUND: As EUCAST epidemiological cut-off values (ECOFFs) are not yet established for Candida auris, a multicentre study was conducted to determined (ECOFF) of echinocandins, amphotericin B and flucytosine using a global collection of C. auris isolates.

METHODS: MIC testing was performed in five centres according to the E.Def 7.4 reference methodology for anidulafungin, micafungin, amphotericin B and flucytosine using standard medium, and for rezafungin using standard medium supplemented with 0.002% Tween 20 as per protocol. A geographically diverse collection of 30 clinical C. auris strains with distinct short tandem repeat genotypes belonging to five different clades was tested. MIC distributions were constructed, and ECOFFs were determined on the basis of qualifying distributions according to EUCAST SOP 10.2 and using the ECOFFinder software, derivatization method and visual inspection.

RESULTS: The centre-specific modal MICs were: 0.008-0.03 mg/L for rezafungin, 0.016-0.06 mg/L for anidulafungin, 0.03-0.06 mg/L for micafungin, 0.5-1 mg/L for amphotericin B and 0.125-0.25 mg/L for flucytosine, and all complied with the EUCAST criterion of being within ±1 2-fold dilution from the most common modal MIC. Consensus EUCAST ECOFFs of 0.125 mg/L for rezafungin, 0.25 mg/L for anidulafungin and micafungin, 0.5 mg/L for flucytosine and 2 mg/L for amphotericin B were established.

CONCLUSIONS: EUCAST ECOFFs have been determined for rezafungin, anidulafungin, micafungin, amphotericin B and flucytosine. They can be adopted to identify non-wild-type isolates and assist clinical breakpoint setting in the future when clinical outcome-MIC data are available.