A combination approach to treating fungal infections

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...

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Bibliographic Details
Published in:Scientific reports 2015-11, Vol.5 (1), p.17070-17070, Article 17070
Main Authors: Shrestha, Sanjib K., Fosso, Marina Y., Garneau-Tsodikova, Sylvie
Format: Article
Language:English
Subjects:
631/326/193
631/326/22
Antifungal Agents - pharmacology
Candida albicans - drug effects
Candida albicans - growth & development
Cell Line, Tumor
Cell Survival - drug effects
Drug Resistance, Fungal - drug effects
Drug Synergism
Drug Therapy, Combination
Epithelial Cells - cytology
Epithelial Cells - drug effects
Fluconazole - pharmacology
Humanities and Social Sciences
Humans
Itraconazole - pharmacology
Microbial Sensitivity Tests
multidisciplinary
Science
Species Specificity
Tobramycin - pharmacology
Triazoles - pharmacology
Voriconazole - pharmacology
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Summary: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, C 12 and C 14 , were shown to display antifungal activities. Herein, the antifungal synergy of C 12 and C 14 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 C 12 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, C 14 exhibited synergistic growth inhibition of all C. albicans strains, except C. albicans MYA-2876 by ITC. The combinations of FLC- C 14 and VOR- C 14 showed synergistic antifungal effect against three C. albicans and four C. albicans strains, respectively. Finally, synergism between C 12 / C 14 and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining C 12 or C 14 with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep17070