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

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Date
2021-06-23
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Frontiers in Cellular and Infection Microbiology, 11, 695240.
Abstract
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.
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Gerlach, E. S., Altamirano, S., Yoder, J. M., Luggya, T. S., Akampurira, A., Meya, D. B., ... & Nielsen, K. (2021). ATI-2307 exhibits equivalent antifungal activity in Cryptococcus neoformans clinical isolates with High and low Fluconazole IC50. Frontiers in Cellular and Infection Microbiology, 11, 695240.