Antifungal activity of diphenyl diselenide alone and in combination with itraconazole against Sporothrix brasiliensis

Abstract

Sporothrix brasiliensis is the main agent of feline and zoonotic sporotrichosis. Given the scarcity of options for sporotrichosis treatment and the promising activity of diphenyl diselenide (PhSe)2 against a diversity of fungal pathogens, this study aimed to evaluate the in vitro susceptibility of Sporothrix brasiliensis to (PhSe)2 alone and in combination with itraconazole (ITC). Forty clinical isolates of S. brasiliensis were subjected to broth microdilution method to evaluate their susceptibility to (PhSe)2 in concentrations ranging between 0.25 and 128 μg/ml, and to ITC (0.0313-16 μg/ml) following the protocol of the Clinical and Laboratory Standards Institute (CLSI, 2008). All of these isolates were also used to evaluate the interaction between these drugs by checkerboard technique. Geometric mean of (PhSe)2 MIC values was 12.12 μg/ml, ranging from 4 to 32 μg/ml, and for ITC was 0.37 μg/ml (0.125 to 1 μg/ml). Benefic effect (additive or synergistic) in the interaction test between (PhSe)2 and ITC occurs in 73% (29/40) of the isolates. The promising (PhSe)2 in vitro activity against S. brasiliensis suggests that it may not only be a potential alternative therapy but also be used as a combination with ITC, which is the first choice of therapy to sporotrichosis.