Evaluation of activity and toxicity of combining clioquinol with ciclopirox and terbinafine in alternative models of dermatophytosis.

Dermatophytosis is a superficial fungal infection that affects humans and is very common in small animals. The treatment using the most commonly used antifungals is failing, and new therapeutic alternatives are required to combat the resistance of these fungal infections. Previous studies by the group have shown that clioquinol is an important therapeutic alternative in the treatment of dermatophytosis. The object was to conduct studies of antidermatophytic activity and the irritant potential from the double and triple combinations of clioquinol, terbinafine and ciclopirox in ex vivo and in vivo alternative models. To evaluate the irritant potential of antifungal combinations, the alternative HET-CAM method (chicken egg test chorioallantoic membrane) was used. Ex vivo models were used to assess the effectiveness of antifungal combinations, using pig hooves and veterinary fur. Any possible tissue damage was to assess through in histopathology of swine ears. HET-CAM results showed that all combinations can be classified as non-irritating, corroborated by the results of the histopathological evaluation of the pig's ear skin. Only the double combinations managed to remove 100% of the colony-forming units (CFU) formed on the pig's hooves. The clioquinol + terbinafine combination and the triple combination were more effective than clioquinol + ciclopirox in eradicating the preformed biofilm in fur of veterinary origin. These results show the potential of formulations of clioquinol in combination with antifungals for use in humans and in the veterinary field to combat dermatophytosis, as an important alternative therapy, for use in the near future.

Rational selection of antifungal drugs to propose a new formulation strategy to control Candida biofilm formation on venous catheters.

INTRODUCTION: Infections associated with medical devices are often related to colonization by Candida spp. biofilm; in this way, numerous strategies have been developed and studied, mainly in order to prevent this type of fungal growth. AIM: Considering the above, the main objective of the present study is to make a rational choice of the best antifungal therapy for the in vitro treatment of the biofilm on venous catheters, proposing an innovative formulation of a film-forming system to coat the surface in order to prevent the formation of biofilms. METHODOLOGY: Anidulafungin, fluconazole, voriconazole, ketoconazole, amphotericin B, and the association of anidulafungin and amphotericin B were tested against biofilms of C. albicans, C. tropicalis, and C. parapsilosis strains in microtiter plates and in a polyurethane catheter. Besides, anidulafungin, amphotericin B, and the combination of both were incorporated in a film-forming system and were evaluated against biofilm. RESULTS: The superior activity of anidulafungin was demonstrated in relation to the other antifungal agents. Although amphotericin B showed good activity, high concentrations were required. The combination showed a synergistic action, in solution and in the formulation, showing excellent results, with activity above 90%. CONCLUSION: Due to the superiority of anidulafungin and the synergistic activity of the combination, these alternatives were the most promising options for use in a formulation proposal as a new strategy to combat the Candida spp. biofilm. These formulations demonstrated high in vitro performance in the prevention of biofilms, indicating that they are candidates with great potential for in vivo tests.