In vitro antidermatophytic synergism of double and triple combination of clioquinol with ciclopirox and terbinafine.

BACKGROUND: Dermatophytoses are the most frequent fungal infections worldwide and there have been described clinical resistance to the commonly used antifungals. Clioquinol is an antimicrobial that had the oral formulations withdrawn from the market in the 70s due to the report of neurotoxicity and recently has been considered as an effective alternative for the treatment of dermatophytosis. OBJECTIVES: To evaluate the effect of the double and triple association between clioquinol with terbinafine and ciclopirox on clinical isolates of dermatophytes. The cytotoxicity of these associations on human leukocytes was also verified. METHODS: Checkerboard method was used to evaluate the interaction between antifungal agents. Time-kill assay was used to verify fungicidal action and evaluate the combination with greater effect for TRU47 isolate. Cell viability was assessed by loss of integrity of the leukocyte membrane in order to verify the toxicity. RESULTS: Synergistic interaction was observed in 42% of isolates when terbinafine was associated with clioquinol and in 50% of isolates when ciclopirox was associated with clioquinol. The triple association resulted in synergistic interaction for 75% of the isolates. Clioquinol + terbinafine and triple combination were more effective for TRU47 isolate, and the combinations exhibited a time-dependent fungicidal effect. Furthermore, the results of cell viability demonstrated that clioquinol and terbinafine combination is not cytotoxic to human leukocytes. CONCLUSIONS: Clioquinol in combination with antifungals in the treatment of dermatophytosis can be a therapeutic strategy to overcome problems related to resistance, action spectrum and toxicity of the antifungal drugs used in the clinic.

Fungal infection models: Current progress of ex vivo methods.

Experimental alternative ex vivo models that simulate infectious processes in vivo are of fundamental importance for the evaluation of new drugs, since in some cases, their execution does not depend on the approval of an ethics committee in research. Although studies using alternative infectious models to evaluate the efficacy of antifungal molecules have been increasingly described and reported, there is no critical consensus that establishes the most appropriate ones regarding the type of infection. Numerous studies contemplate ex vivo protocols of fungal infections on nails, corneas, dentinal tubules and skin and reveal counterpoints and concordances not yet finely confronted. In this minireview, we propose a critical analysis of the main ex vivo models of fungal infections for the evaluation of new antifungal candidates for both topical and systemic use, as opposed to the advantages and disadvantages of the traditional in vivo models employed in preclinical research.