Avaliação, in vitro, da atividade antifúngica de miltefosina e iodeto de potássiofrente à espécies do complexo Sporothrix schenckii na forma leveduriforme

Abstract

Sporotrichosis is a subcutaneous, cosmopolitan mycosis caused by dimorphic fungi belonging to the Sporothrix schenckii complex, found predominantly in tropical and subtropical areas of Latin America. Miltefosine (MIL) is a chemotherapeutic class of antineoplastic agents. Subsequently, its antiparasitic action was demonstrated, and its antifungal potential was verified in vitro. This study aimed to analyze the planktonic sensitivity of S. schenckii complex species in the yeast form to miltefosine, determining the minimum inhibitory concentration (MIC). Eighteen strains were used in the yeast form of S. schenckii. S. brasiliensis (n = 10), S. mexicana (n = 4), S. schenckii stricto sensu (n = 2), and S. globosa (n = 2). Miltefosine (MIL) and potassium iodide (KI) tested at concentrations of 0.0313-16 μg / mL were used as test drugs. Amphotericin B (AMB) and Itraconazole (ITC) were included as control drugs, and were tested at concentrations of 0.0313 to 16 μg / mL, respectively. Dilutions were prepared in RPMI. Sensitivity tests were performed using the 96-well plate broth microdilution method for the yeast form. The plankton sensitivity test aims to obtain the minimum inhibitory concentration (MIC) values. The inoculums were made in saline solution and adjusted on the McFarland scale 1. Subsequently, dilutions were made in RPMI, for final adjustment of the inoculum, at concentrations 1 to 5 x 103 CFU / mL. Samples were tested in duplicate, and the results read visually after the incubation period of 96 h at 37 ° C. AMI MIC was considered the lowest concentration capable of inhibiting 100% (MIC100) of fungal growth, MIL as the lowest concentration capable of inhibiting 50% (MIC50), 80% (MIC80), and 100% fungal growth , and from ITC to MIC as capable of inhibiting 100% fungal growth when compared to growth control. All strains of Sporothrix schenckii were inhibited by the drugs miltefosine and potassium iodide. For the yeast form, we obtained the following MIC values: 62.5 to 125 mg / mL for KI, 0.125 to 2 μg / mL for MIL; 0.125 to 1 μg / mL for ITC; 0.0312 at 1 μg / mL for AMB. The following significant KI inhibition values were shown in MIC with KI> AMB, ITC and MIL (p <0.0001) for CIM80 and CIM50, with KI> ITC and MIL (p <0.0001). It is concluded that all strains of S. schenckii were inhibited by Miltefosine proving their antifungal activity in vitro and by Potassium Iodide.