Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Hospital Clínico Veterinario, Universidad Complutense de Madrid, Madrid, Spain.
Med Mycol. 2019 Feb 1;57(2):196-203. doi: 10.1093/mmy/myy009.
Combination therapy has become popular in clinical practice, but limited data on the effects of combinations of antifungal agents is still available for most fungal pathogens. We studied the in vitro response of 30 genetically diverse clinical strains of the basidiomycetous lipophilic yeast Malassezia pachydermatis obtained from cases of canine otitis to several amphotericin B (AMB)-azole combinations. Broth microdilution checkerboard tests revealed that AMB antagonized the effects of itraconazole (ITC) and voriconazole (VRC) in 50% and 6.7% of the strains, respectively, but did not interact with fluconazole or posaconazole (fractional inhibitory concentration index (FICI) values were <4 in all cases). Subsequent Etest-based assays performed for a subset of strains did not confirm the antagonism between AMB and ITC or AMB and VRC. In summary, the results of this study suggest that antagonistic combination effects between AMB and azoles might occur when tested against M. pachydermatis. Nevertheless, as observed for other fungi, different in vitro analyses yielded contrasting results, and the response to AMB-azole combinations was compound- and strain-dependant.
联合治疗在临床实践中已经很流行，但对于大多数真菌病原体，仍然缺乏关于抗真菌药物联合使用效果的有限数据。我们研究了从犬耳炎病例中获得的 30 株遗传多样性的担子菌亲脂酵母马拉色菌的体外反应，这些菌株对几种两性霉素 B（AMB）-唑类联合药物的反应。肉汤微量稀释棋盘试验显示，AMB 分别拮抗伊曲康唑（ITC）和伏立康唑（VRC）在 50%和 6.7%的菌株中的作用，但不与氟康唑或泊沙康唑相互作用（所有情况下的分数抑菌浓度指数（FICI）值均<4）。随后对部分菌株进行的基于 Etest 的检测并未证实 AMB 与 ITC 或 AMB 与 VRC 之间的拮抗作用。总之，这项研究的结果表明，在针对马拉色菌时，AMB 和唑类之间可能存在拮抗联合作用。然而，与其他真菌一样，不同的体外分析产生了相反的结果，并且对 AMB-唑类联合药物的反应取决于化合物和菌株。
