AUTHOR=Gerlach Elliot S. , Altamirano Sophie , Yoder J. Marina , Luggya Tony S. , Akampurira Andrew , Meya David B. , Boulware David R. , Rhein Joshua , Nielsen Kirsten 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.695240

DOI=10.3389/fcimb.2021.695240

ISSN=2235-2988

ABSTRACT=<p>Half maximal inhibitory concentrations (IC<sub>50</sub>) to the experimental drug ATI-2307 and complete inhibition (IC<sub>90</sub>) of the common clinically used antifungal drug amphotericin B were determined by microbroth dilution assay for a collection of 69 clinical isolates of <italic>Cryptococcus neoformans</italic> from Uganda that had high fluconazole IC<sub>50</sub> values. The majority of the clinical isolates tested had fluconazole IC<sub>50</sub> at or above 8 µg/mL, but were susceptible to both amphotericin B (IC<sub>90</sub> ≤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.</p>