Department of Clinical Pharmacy, Shandong Provincial Qianfoshan Hospital, Shandong University. Jinan, 250014, People's Republic of China; School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China.
Department of Pharmacy, Shandong Provincial Third Hospital, Jinan, 250014, People's Republic of China.
Int J Antimicrob Agents. 2020 Aug;56(2):106030. doi: 10.1016/j.ijantimicag.2020.106030. Epub 2020 May 23.
The number of invasive fungal infections has increased dramatically over recent years, leading to high morbidity and mortality of immunocompromised patients. Candida albicans is the most common cause of life-threatening disseminated candidiasis among invasive fungal infections. Resistance of C. albicans against conventional antifungals is frequently reported. Treatment with a combination of antifungal and non-antifungal agents is often considered in the aim to overcome drug resistance. This study shows for the first time that the combination of ginkgolide B (GB) and fluconazole (FLC) increases the sensitivity of resistant C. albicans to FLC. In vitro studies indicated that the drug combination had a synergistic effect on C. albicans in both planktonic cells and biofilms within 12 h. In vivo efficacy of this drug combination was evaluated using the Galleria mellonella infection model. Survival rate, fungal burden, and histological examination were determined. Studies indicated that the antifungal effects of GB in combination with FLC might be associated with inhibition of hyphal growth, disruption of intracellular calcium, and inhibition of drug efflux pumps. The results indicate a promising solution for overcoming drug resistance of C. albicans and expanding the clinical application of existing drugs.
近年来，侵袭性真菌感染的数量急剧增加，导致免疫功能低下患者的发病率和死亡率居高不下。白色念珠菌是侵袭性真菌感染中导致危及生命的播散性念珠菌病的最常见原因。白色念珠菌对常规抗真菌药物的耐药性经常被报道。为了克服耐药性，常考虑使用抗真菌药物和非抗真菌药物的联合治疗。本研究首次表明，白果内酯 B（GB）和氟康唑（FLC）的联合使用增加了耐药白色念珠菌对 FLC 的敏感性。体外研究表明，在 12 小时内，药物联合对浮游细胞和生物膜中的白色念珠菌具有协同作用。使用大蜡螟感染模型评估了这种药物联合的体内疗效。测定存活率、真菌负荷和组织学检查。研究表明，GB 与 FLC 联合使用的抗真菌作用可能与抑制菌丝生长、破坏细胞内钙和抑制药物外排泵有关。结果表明，这为克服白色念珠菌的耐药性和扩大现有药物的临床应用提供了一种有前途的解决方案。
