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.