A Combination Approach to Treating Fungal Infections

Authors

Sanjib K. Shrestha, University of KentuckyFollow
Marina Y. Fosso, University of KentuckyFollow
Sylvie Garneau-Tsodikova, University of KentuckyFollow

Abstract

Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C₁₂ and C₁₄, were shown to display antifungal activities. Herein, the antifungal synergy of C₁₂ and C₁₄ with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains were synergistically inhibited by C₁₂ when combined with azoles, with the exception of C. albicans 64124 and MYA-2876 by FLC and VOR. Likewise, when combined with POS and ITC, C₁₄ exhibited synergistic growth inhibition of all C. albicans strains, except C. albicans MYA-2876 by ITC. The combinations of FLC-C₁₄ and VOR-C₁₄ showed synergistic antifungal effect against three C. albicans and four C. albicans strains, respectively. Finally, synergism between C₁₂/C₁₄ and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining C₁₂ or C₁₄ with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency.

Document Type

Article

Publication Date

11-23-2015

Notes/Citation Information

Published in Scientific Reports, v. 5, article 17070, p. 1-11.

Copyright © 2015, Macmillan Publishers Limited

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Digital Object Identifier (DOI)

http://dx.doi.org/10.1038/srep17070

Funding Information

This work was supported by the National Institutes of Health (NIH) grant AI090048 (to S.G.-T.) and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T.).

Repository Citation

Shrestha, Sanjib K.; Fosso, Marina Y.; and Garneau-Tsodikova, Sylvie, "A Combination Approach to Treating Fungal Infections" (2015). Pharmaceutical Sciences Faculty Publications. 63.
https://uknowledge.uky.edu/ps_facpub/63