In vitro activity of isavuconazole, ravuconazole, and comparison of the Sensititre YeastOne and CLSI broth microdilution methods against clinical isolates of Trichosporon species.

Abstract

This study aimed to evaluate the in vitro activity of isavuconazole and ravuconazole against clinical Trichosporon isolates. Additionally, we assessed the performance of the Sensititre YeastOne (SYO) assay compared to the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) method for antifungal susceptibility testing. A total of 267 Trichosporon clinical isolates were collected from multiple centers in Taiwan between 2008 and 2020. The MIC values for amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole obtained using the CLSI BMD were compared to those determined using SYO. Among the seven antifungal agents tested using the CLSI BMD method, T. asahii isolates (n = 224) exhibited significantly higher MICs for fluconazole, voriconazole, isavuconazole, and ravuconazole compared to non-T. asahii isolates (n = 43) (p < 0.05). Across all isolates, voriconazole demonstrated the lowest geometric mean (GM) MIC (0.06 mg/L). For T. asahii, the MIC₅₀, MIC₉₀, and GM MICs for posaconazole, isavuconazole, and ravuconazole were within ±1 twofold dilution, while mode MICs showed slightly greater variation (MIC₅₀, MIC₉₀, mode, and GM MICs were 0.25, 0.5, 0.5, and 0.28 mg/L; 0.12, 0.5, 0.12, and 0.17 mg/L; and 0.25, 0.5, 0.25, and 0.21 mg/L, respectively). The consistency of the MIC measurements between the SYO and CLSI BMD methods was assessed for amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole. The highest agreement within ±1 twofold dilution for T. asahii isolates was observed for posaconazole (94.2%). The essential agreement within ±2 twofold dilutions between both methods for all drugs was >97%. In conclusion, isavuconazole and ravuconazole demonstrated favorable in vitro activity against clinical Trichosporon isolates, while the SYO assay showed good concordance with the CLSI BMD method.IMPORTANCEInvasive infections caused by Trichosporon species pose significant therapeutic challenges, primarily due to their intrinsic resistance to echinocandins and the limited availability of effective treatment options. This study provides essential data on the in vitro activity of newer azoles and comprehensively evaluates the performance and concordance of the Sensititre YeastOne (SYO) and CLSI broth microdilution (BMD) methods. The current study analyzed 267 Trichosporon clinical isolates collected from multicenter settings in Taiwan. Our results demonstrate that both isavuconazole and ravuconazole exhibit favorable in vitro activities against Trichosporon species. For T. asahii, the essential agreement between the SYO and CLSI BMD methods exceeded 97% for all tested antifungal agents, indicating that the SYO method exhibits good concordance for most Trichosporon species. Further investigations are warranted to validate these findings and to assess their clinical implications.