Aix-Marseille Université, IRD, APHM, MEPHI, Marseille, France.
IHU Méditerranée Infection, Marseille, France.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.00263-19. Print 2019 Oct.
The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against spp. Primary screening of a Prestwick Chemical library against ATCC 90028 and fluconazole-resistant strains was performed. Subsequently, we evaluated the responses of 100 sp. strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin resistance. We studied time-kill curves and performed a checkerboard assay for a ribavirin-antifungal combination study. Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had antifungal activity against 63 strains, including strains of , , and , with MICs ranging from 0.37 to 3.02 μg/ml, while MICs for , , , and some strains remained high (≥24.16 μg/ml). No relation was observed between efflux pump activity and ribavirin resistance. Ribavirin exhibited fungistatic activity against multidrug-resistant (MDR) and fungicidal activity against a strain. In addition, ribavirin acted synergistically with azoles against strains for which ribavirin MICs were <24.4 μg/ml. This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti- drug.
在临床环境中使用抗真菌药物受到耐药性和不良反应的出现的限制。因此，迫切需要开发新的药物来加强侵袭性真菌感染的治疗。本研究旨在描述利巴韦林作为一种辅助治疗方法在治疗 属中的潜在用途。我们对普雷斯威克化学库进行了初步筛选，以对抗 ATCC 90028 和氟康唑耐药的 株。随后，我们使用 CLSI 推荐的肉汤微量稀释法评估了利巴韦林（一种抗病毒药物）对 100 株 属菌株的反应。我们检查了外排泵活性在利巴韦林耐药性发展中的参与情况。我们研究了时间杀伤曲线，并进行了利巴韦林-抗真菌联合研究的棋盘试验。鉴定出 21 种非标准抗真菌化合物，包括利巴韦林。利巴韦林对 63 株菌株具有抗真菌活性，包括 、 、和 属的菌株，MIC 范围为 0.37 至 3.02μg/ml，而对 、 、 和一些 属的菌株的 MIC 仍然较高（≥24.16μg/ml）。未观察到外排泵活性与利巴韦林耐药性之间存在关系。利巴韦林对多药耐药（MDR） 和一株 属的菌株表现出抑菌活性，并对一株 属的菌株表现出杀菌活性。此外，对于利巴韦林 MIC 值<24.4μg/ml 的 属菌株，利巴韦林与唑类药物联合具有协同作用。本研究强调了利巴韦林作为一种辅助抗真菌药物，单独或与其他抗真菌药物联合使用的潜在临床应用。
