Antifungal susceptibility profile of clinically relevant species of the genus <i>Sporothrix:</i> establishment of Epidemiological Cutoff Values (ECVs) according to CLSI broth microdilution methodology

Abstract Sporotrichosis is a globally distributed subcutaneous mycosis caused mainly by Sporothrix brasiliensis , S. schenckii , and S. globosa . Cat-transmitted sporotrichosis, primarily caused by S. brasiliensis in South America and to a lesser extent by S. schenckii in Southeast Asia, is emerging as a significant public health concern, due its outbreak potential. Itraconazole is the first-choice drug for treatment of human and cats, but reduced susceptibility has been reported based on previously proposed epidemiological cut-off values (ECVs). To support resistance surveillance, we aimed to establish CLSI-endorsed ECVs for these clinically relevant Sporothrix species. A total of 3,588 minimum inhibitory concentration (MIC) values for seven antifungal agents (amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, olorofim, and terbinafine) were obtained from 19 international laboratories. Four of seven antifungals met the CLSI M57 guidelines criteria to determine the ECV. Established ECVs for amphotericin B were found to be high with 8 µg/mL for S. brasiliensis and S. globosa , and 4 µg/mL for S. schenckii . Itraconazole ECVs were 4 µg/mL for S. brasiliensis and S. schenckii . Posaconazole ECVs were 4 µg/mL for all three species (tentative for S. globosa ), while the terbinafine ECV for S. brasiliensis was 0.12 µg/mL. Olorofim demonstrated good in vitro activity, particularly against S. brasiliensis . Overall, this study establishes validated ECVs for key antifungals against Sporothrix species and identifies a low prevalence of non-wild type (NWT) isolates, supporting ongoing antifungal resistance monitoring.

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