Department of Clinical Medicine, School of Medicine, Post-Graduation Program in Medicine Science, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
J Med Microbiol. 2014 Jul;63(Pt 7):936-944. doi: 10.1099/jmm.0.073478-0. Epub 2014 Apr 10.
Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs.
近平滑假丝酵母复合体由三个密切相关的种组成，即近平滑假丝酵母（Candida parapsilosis）、中间假丝酵母（Candida metapsilosis）和鲍氏假丝酵母（Candida orthopsilosis）。在过去的十年中，广泛分布的近平滑假丝酵母对唑类药物和卡泊芬净的抗药性已引起全球关注。本研究评估了抗真菌药物与钙调磷酸酶抑制剂环孢素 A（Cys）对临床来源的近平滑假丝酵母复合体浮游细胞和生物膜的协同作用。根据临床和实验室标准协会的指南，通过微量稀释法进行两性霉素、氟康唑、伏立康唑、卡泊芬净和 Cys 的药敏试验。采用棋盘微量稀释法评估抗真菌药物与 Cys 联合对浮游细胞的协同作用。在微量滴定板上评估抗真菌药物与 Cys 联合对成熟生物膜的作用。在种间未观察到抗真菌敏感性模式的差异，但与 C. orthopsilosis 和 C. metapsilosis 相比，C. parapsilosis stricto 对 Cys 的敏感性更高。在近平滑假丝酵母复合体中观察到抗真菌药物与 Cys 的协同作用。抗真菌药物与 Cys 的组合能够预防生物膜形成，并对 C. parapsilosis stricto、C. metapsilosis 和 C. orthopsilosis 的成熟生物膜显示出抑制作用。这些结果增强了钙调磷酸酶抑制作为提高抗真菌药物效率的一种有前途的方法的潜力。
