Establishment of epidemiological cutoff values for yeast-phase Talaromyces marneffei against six antifungal agents: a multicenter study in China

This study aimed to establish epidemiological cutoff values (ECVs) for amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole against Talaromyces marneffei ( T. marneffei ) using the CLSI broth microdilution method. Antifungal susceptibility testing of 207 T. marneffei isolates was performed independently at five laboratories across China according to CLSI M27-A4 guidelines. Minimum inhibitory concentration (MIC) distributions were analyzed using ECOFFinder software (version 2.1), and ECVs were set at the upper MIC limit encompassing 97.5% of the modeled wild-type (WT) population. ECVs were determined as follows: amphotericin B (AMB) 8 µg/mL, voriconazole (VRC) 0.03 µg/mL, itraconazole (ITC) 0.125 µg/mL, posaconazole (POS) 0.06 µg/mL, isavuconazole (ISA) 0.125 µg/mL, and fluconazole (FLC) 8 µg/mL. MIC distributions for all six agents conformed well to the fitted models (normal or log-normal), supporting the validity of ECV determination. No non-WT isolates were detected for amphotericin B, whereas non-WT rates for azoles were 15.5% (voriconazole), 8.45% (itraconazole), 6.37% (posaconazole), 3.0% (fluconazole), and 1.02% (isavuconazole). Among voriconazole non-WT isolates, all were from patients with prior voriconazole exposure. This study provides the first standardized ECVs for T. marneffei against six key antifungal agents. The data establish a reference framework for antifungal susceptibility testing and resistance surveillance and highlight the need for continued monitoring of azole susceptibility in this pathogen.