How to interpret MICs of amphotericin B, echinocandins and flucytosine against Candida auris (Candidozyma auris) according to the newly established EUCAST breakpoints.

Abstract

Background: Candida auris (Candidozyma auris) has emerged as an important pathogen across all continents, with clonal outbreaks and hospital transmissions. Most isolates are fluconazole resistant and variable resistance rates are reported for amphotericin B and echinocandins.

Objectives: The aim was to present an overview of the newly established ECOFFs and antifungal breakpoints against C. auris and the supporting evidence.

Sources: This document is based on the recently updated EUCAST rationale documents, clinical breakpoint and ECOFF documents.

Content: An alternative approach was adopted for ECOFF setting of C. auris to avoid MIC distributions dominated by isogenic outbreak strains. A carefully selected strain collection of 30 isolates from 11 countries, representing five clades and 21 unique genotypes, was shared among five individual laboratories. MICs were determined with the EUCAST E.Def 7.4 methodology providing five non-clonal datasets well above the required ≥100 total MICs per drug. Available PK-PD and clinical data were reviewed. The following ECOFFs and breakpoints were established for C. auris: amphotericin B: ECOFF: 2 mg/L, S: ≤ 0.001 mg/L, R: >2 mg/L; implying that the entire wild-type distribution is "susceptible, Increased exposure" (I) (increased dose: 5 mg/kg liposomal amphotericin B daily); anidulafungin and micafungin: ECOFFs: 0.25 mg/L, S: ≤ 0.25; R: >0.25; rezafungin: ECOFF: 0.125 mg/L; and flucytosine: ECOFF: 0.5 mg/L. Importantly, notable MIC variations have been reported for C. auris and some agents across commercial tests. Consequently, important detailed guidance is provided on how to validate your MIC test in house before adopting the EUCAST breakpoints for MIC interpretation.