Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Mycoses. 2020 Sep;63(9):993-1001. doi: 10.1111/myc.13127. Epub 2020 Jul 1.
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 Clioquinol is an antimicrobial that had the oral formulations withdrawn from the market in the 70s due to the report of neurotoxicity and recently has been considered as an effective alternative for the treatment of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.
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.
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.
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.
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.
皮肤癣菌病是全球最常见的真菌感染，临床上已描述了对常用抗真菌药物的耐药性。卤倍他索是一种具有抗菌作用的药物，由于其报告的神经毒性，该药物的口服制剂已于 20 世纪 70 年代从市场上撤出，最近被认为是治疗皮肤癣菌病的有效替代药物。
评估卤倍他索与特比萘芬和环吡酮联合应用对皮肤癣菌临床分离株的疗效。还验证了这些组合对人白细胞的细胞毒性。
采用棋盘法评估抗真菌药物之间的相互作用。采用时间杀伤试验验证杀菌作用，并评估对 TRU47 分离株具有更大效果的组合。通过白细胞细胞膜完整性丧失来评估细胞活力，以验证毒性。
当特比萘芬与卤倍他索联合使用时，42%的分离株观察到协同作用，当环吡酮与卤倍他索联合使用时，50%的分离株观察到协同作用。三重联合对 75%的分离株产生协同作用。卤倍他索+特比萘芬和三联组合对 TRU47 分离株更有效，组合表现出时间依赖性杀菌作用。此外，细胞活力的结果表明，卤倍他索和特比萘芬联合使用对人白细胞没有细胞毒性。
在治疗皮肤癣菌病时，卤倍他索与抗真菌药物联合使用可能是一种治疗策略，可以克服与耐药性、作用谱和临床使用的抗真菌药物毒性相关的问题。
