Oxythiamine improves antifungal activity of ketoconazole evaluated in canine Malassezia pachydermatis strains.

Abstract

Malassezia pachydermatis is an opportunistic yeast involved in skin and ear canal infections of dogs and cats. Reports suggest that strains of M.pachydermatis resistant to commonly used antifungal agents may be emerging. Therefore, new therapeutic strategies should be explored. The synergistic effect of oxythiamine (OT) and ketoconazole (KTC) was analysed using a reference strain and field isolates (n=66) of M.pachydermatis. Hydrogel formulations containing these components also were evaluated. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of OT, KTC and their mixtures were determined by a broth macrodilution method. The antifungal effects of hydrogel formulations were determined by a plate diffusion method. The MIC and MFC values of OT were in the range 0.08×103 to 10×103 mg/L. All M.pachydermatis strains showed higher susceptibility to KTC (MICs and MFCs in the range 0.04-0.32mg/L). Formulations that combined OT and KTC showed a synergistic effect for all tested isolates (n=66). Hydrogels that contained OT at a concentration of 10×103 or 20×103 mg/L and KTC at the concentration of 0.1×103 mg/L showed a stronger effect than a commercially available product with KTC alone (20×103 mg/L). Synergy of these drugs may allow for successful topical treatment which utilizes lower doses of KTC without changing its therapeutic effectiveness. Hydrogel formulations proved to be attractive drug carriers for potential topical use.