Objective: Given the current scarce options for sporotrichosis treatment added to the promising antifungal effect of diphenyl diselenide (PhSe)2 against a variety of fungal species, this study aimed to evaluate the in vitro susceptibility of  Sporothrix brasiliensis to the (PhSe)2 and to the combination of this compound with itraconazole (ITC). Methods: 40 clinical strains of S. brasiliensis were studied, being 20 from feline sporotrichosis cases and 20 from human cases. An inoculum preparation was performed with subsequent microdilution technique following the Clinical and Laboratory Standards Institute protocol (CLSI, 2008) to determine the Minimal Inhibitory Concentration (MIC) (inhibition of 100% of the fungal growth). Compounds concentration tested ranged between 0.25 to 128 µg/mL for (PhSe)2 and 0.0313 to 16 µg/mL for ITC. The combination of (PhSe)2 and ITC was evaluated throughout a checkerboard assay determining the Fractional Inhibitory Concentration Index (FICI). All tests were performed in duplicate. Geometric mean (GM) of MIC values, MIC50 and MIC90 were calculated for each drug tested. Additionally, a Kruskal-Wallis test was done to compare the MIC values of (PhSe)2 and ITC regarding its origin (feline x human), using the statistic software SPSS 20.0 and considering significant p<0.05 . Results: MIC values for the 40 isolates tested ranged from 4 to 32 µg/mL for (PhSe)2 and from 0.125 to 1 µg/mL for ITC. GM, MIC50 and MIC90 of (PhSe)2 and ITC were 12.13, 8 and 32 µg/mL, and 0.37, 0.5 and 1 µg/mL, respectively. Comparing MIC values of (PhSe)2 and ITC among the origin of the isolate (feline or human), none significant difference was found (p>0,05), although the geometric average MIC for both drugs was higher in human isolates [13.45 and 0.42 for (PhSe)2 and ITC, respectively] than in felines [10.93 and 0.32 for (PhSe)2 and ITC, respectively]. In combination, (PhSe)2 and ITC did not show antagonistic relationship in none isolates tested, being indifferent in 27% (11/40) and showing beneficial effects [additive (n=26) or synergistic (n=3) relationship] in 73% (29/40) of them. Conclusion: Diphenyl diselenide showed a promising in vitro activity against the S. brasiliensis species. In addition, the high percentage of positive effects (73%) in it combination with itraconazole, suggest that it also has a further potential as an adjuvant therapy with antifungal agents.

Antifungal activity of Diphenyl Diselenide alone and in combination with itraconazole against Sporothrix brasiliensis