Antifungal Activity of Minocycline and Azoles Against Fluconazole-Resistant Candida Species

• Published in: Frontiers in microbiology 2021-05, Vol.12, p.649026-649026
• Main Authors: Tan, Jingwen, Jiang, Shaojie, Tan, Lihua, Shi, Haiyan, Yang, Lianjuan, Sun, Yi, Wang, Xiuli
• Format: Article
• Language: English
• Subjects: antifungal; azole; Candida auris; fluconazole resistant Candida spp; Microbiology; minocycline; synergy
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2021.649026

Candida species are the most common fungal pathogens to infect humans, and can cause life-threatening illnesses in individuals with compromised immune systems. Fluconazole (FLU) is the most frequently administered antifungal drug, but its therapeutic efficacy has been limited by the emergence of drug-resistant strains. When co-administered with minocycline (MIN), FLU can synergistically treat clinical Candida albicans isolates in vitro and in vivo . However, there have been few reports regarding the synergistic efficacy of MIN and azoles when used to treat FLU-resistant Candida species, including Candida auris . Herein, we conducted a microdilution assay wherein we found that MIN and posaconazole (POS) showed the best in vitro synergy effect, functioning against 94% (29/31) of tested strains, whereas combinations of MIN+itraconazole (ITC), MIN+voriconazole (VOR), and MIN+VOR exhibited synergistic activity against 84 (26/31), 65 (20/31), and 45% (14/31) of tested strains, respectively. No antagonistic activity was observed for any of these combinations. In vivo experiments were conducted in Galleria mellonella , revealing that combination treatment with MIN and azoles improved survival rates of larvae infected with FLU-resistant Candida . Together, these results highlight MIN as a promising synergistic compound that can be used to improve the efficacy of azoles in the treatment of FLU-resistant Candida infections.