Revision of EUCAST breakpoints: consequences for susceptibility of contemporary Danish mould isolates to isavuconazole and comparators.

BACKGROUND EUCAST recently revised the definition of the 'I' category from 'intermediate' to 'susceptible, increased exposure'. Consequently, all current antifungal breakpoints have been reviewed and revised breakpoints (v 10.0) have been released. OBJECTIVES We investigated isavuconazole and comparator MICs (mg/L) against contemporary moulds and the consequences of the breakpoint revision for susceptibility classification. METHODS Six hundred and ninety-six Aspergillus and 46 other moulds were included. EUCAST E.Def 10.1 azole resistance screening was performed for Aspergillus fumigatus and E.Def 9.3.1 testing of non-susceptible A. fumigatus and other moulds. Most non-wildtype/resistant isolates underwent cyp51A sequencing. RESULTS Isavuconazole MIC50/MIC90s were ≤1/≤2 mg/L for Aspergillus flavus, A. fumigatus and Aspergillus nidulans versus 2/4 mg/L for Aspergillus niger and 2/16 mg/L for Aspergillus terreus. For the remaining moulds, MICs were highest for Fusarium (16 to >16 mg/L), lowest for dermatophytes (0.06-0.5 mg/L) and in between for Mucorales and others (1 to >16 mg/L). A very strong isavuconazole-voriconazole MIC correlation was found for A. fumigatus (Pearson r = 0.888) and itraconazole-posaconazole correlation for A. fumigatus (r = 0.905) and A. terreus (r = 0.848). For A. fumigatus, the revised breakpoints lowered isavuconazole resistance (22.6% to 7.7%, P  4, 4 and 2 mg/L, respectively. CONCLUSIONS Isavuconazole displays broad anti-mould activity. The revised breakpoints result in fewer misclassifications of wildtype isolates without compromising detection of resistant mutants.