Establishment of epidemiological cutoff values for clinically relevant Sporothrix species using CLSI-broth microdilution

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 substantial public health concern due to its outbreak potential. Itraconazole is the first-line drug for the treatment of humans and cats, but reduced susceptibility has been reported based on previously proposed epidemiologi cal cut-off values (ECVs). To support resistance surveillance, we aimed to establish the Clinical and Laboratory Standards Institute (CLSI)-endorsed ECVs for these clinically relevant Sporothrix species. A total of 3,504 minimum inhibitory concentration (MIC) values for six antifungal agents (amphotericin B, itraconazole, posaconazole, voricona zole, isavuconazole, 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. Overall, this study establishes validated ECVs for key antifungals against Sporothrix species and identifies a low prevalence of non-wild-type (NWT) isolates (<10% except for S. schenckii and posaconazole), supporting ongoing antifungal resistance monitoring.