COMPARISON OF YEAST AND FUNGUS FORM IN VITRO SUSCEPTIBILITIES OF SPOROTHRIX SCHENCKII IN MALAYSIA

IN VITRO SUSCEPTIBILITY OF SPOROTHRIX SCHENCKII

Abstract

Sporothrix schenckii causes sporotrichosis, but the sensitivities of this organism’s yeast and fungus forms in Malaysia to antifungals are not well studied. In this study, we aimed to determine the minimum inhibitory concentrations (MIC) of the yeast and fungus forms of S. schenckii obtained clinically to evaluate if there is a difference in susceptibility testing between these two forms: yeast and fungus. We retrospectively reviewed the susceptibilities of 96 clinical specimens of S. schenckii obtained during 2020-2021. Yeast and fungus specimens were identified through microscopic, macroscopic and molecular methods. The susceptibility of each isolate was determined following the Clinical and Laboratory Standards Institute (CLSI) M27-A4 and M38 guidelines. The tested antifungals were amphotericin B, terbinafine, posaconazole, voriconazole, itraconazole, ketoconazole, ravuconazole and isavuconazole. For each antifungal, the geometric mean (GM) MICs, MIC50 and MIC90 were determined. A comparison between the GM MICs for yeast and fungus forms was conducted using the Wilcoxon Sign Rank test with significance set at p<0.05. The GM MICs of amphotericin B, terbinafine, posaconazole, voriconazole, itraconazole, ketoconazole, ravuconazole and isavuconazole against the fungus form were 1.93 µg/ml, 0.13 µg/ml, 0.17 µg/ml, 0.68 µg/ml, 0.20 µg/ml, 0.09 µg/ml, 0.16 µg/ml and 0.18 µg/ml, respectively and against the yeast form were 0.23 µg/ml, 0.05 µg/ml, 0.04 µg/ml, 0.04 µg/ml, 0.04 µg/ml, 0.04 µg/ml, 0.04 µg/ml and 0.04 µg/ml, respectively. The MIC50 and MIC90 for ketoconazole against the fungus form were the lowest at 0.03 µg/ml and 0.5 µg/ml, respectively and the MIC50 and MIC90 against the yeast form were also the lowest at 0.03 µg/ml and 0.06 µg/ml, respectively. The MIC50 and MIC90 of amphotericin B against fungus form were the highest at 4 µg/ml and 16 µg/ml, respectively and against the yeast form were 0.03 µg/ml and 16 µg/ml, respectively. The MICs for each antifungal were significantly higher against the fungus form than the yeast form (p<0.05). The GM MIC and MIC90 results of the tested antifungals were significantly lower against the yeast than the fungus forms, but the MIC50 results were not significantly different between the yeast and fungus forms. However, the best growth form (fungus or yeast) of S. schenckii that should be used for sensitivity testing to best represent the clinical response has yet to be determined. Further studies are needed to determine if these findings can inform clinical decision-making.