ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC50

Frontiers in Cellular and Infection Microbiology

Elliot S. Gerlach¹  J. Marina Yoder¹  Kirsten Nielsen¹  Sophie Altamirano¹  Joshua Rhein²  David R. Boulware²  Andrew Akampurira³  Tony S. Luggya³  David B. Meya³ 

[1] Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States;Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, United States;Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

关键词: ATI-2307;    Cryptococcus;    azole;    antifungal;    susceptibility;    resistance;   

DOI  :  10.3389/fcimb.2021.695240

来源: DOAJ

【 摘 要 】

Half maximal inhibitory concentrations (IC50) to the experimental drug ATI-2307 and complete inhibition (IC90) of the common clinically used antifungal drug amphotericin B were determined by microbroth dilution assay for a collection of 69 clinical isolates of Cryptococcus neoformans from Uganda that had high fluconazole IC50 values. The majority of the clinical isolates tested had fluconazole IC50 at or above 8 µg/mL, but were susceptible to both amphotericin B (IC90 ≤1 μg/mL) and ATI-2307 (IC50 ≤0.0312 µg/mL). No correlation between increased fluconazole minimum inhibitory concentration (MIC) and ATI-2307 or amphotericin B MIC was observed, suggesting that the cellular changes impacting fluconazole susceptibility did not impact the effectiveness of ATI-2307. Our results suggest that ATI-2307 is a promising new antifungal drug for use in the context of high fluconazole or other antifungal drug MICs and/or in combination drug therapy regimens.

【 授权许可】

Unknown