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In vitro combination therapy with isavuconazole against Candida spp.

TitleIn vitro combination therapy with isavuconazole against Candida spp.
Publication TypeJournal Article
Year of Publication2017
AuthorsKatragkou, A., McCarthy M., Meletiadis J., Hussain K., Moradi P. W., Strauss G. E., Myint K. L., Zaw M. H., Kovanda L. L., Petraitiene R., Roilides E., Walsh T. J., & Petraitis V.
JournalMed Mycol
Volume55
Issue8
Pagination859-868
Date Published2017 Nov 01
ISSN1460-2709
KeywordsAmphotericin B, Antifungal Agents, Candida, Candidiasis, Invasive, Drug Synergism, Echinocandins, In Vitro Techniques, Lipopeptides, Microbial Sensitivity Tests, Nitriles, Pyridines, Time Factors, Triazoles
Abstract

Combination therapy may be an alternative therapeutic approach for difficult-to-treat Candida infections with the aim of increasing efficacy of antifungal therapy. Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or polyenes for the treatment of invasive candidiasis has not been studied. We used Bliss independence drug interaction analysis and time-kill assays to examine the in vitro interactions of isavuconazole with amphotericin B or micafungin, an echinocandin, against strains of Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, and Candida krusei. The Bliss independence-based drug interactions modeling showed that the combination of isavuconazole and micafungin resulted in synergistic interactions against C. albicans, C. parapsilosis, and C. krusei. The degree of synergy ranged from 1.8% to 16.7% (mean %ΔΕ value) with the highest synergy occurring against C. albicans (⊙SYN% = 8.8%-110%). Time-kill assays showed that the isavuconazole-micafungin combination demonstrated concentration-depended synergy against C. albicans and C. parapsilosis. The combined interaction by Bliss analysis between isavuconazole and amphotericin B was indifferent for C. albicans, C. parapsilosis, and C. tropicalis while for C. glabrata was antagonistic (-2% to -6%) and C. krusei synergistic (3.4% to 7%). The combination of isavuconazole-amphotericin B by time-kill assay was antagonistic against C. krusei and C. glabrata. Collectively, our findings demonstrate that combinations of isavuconazole and micafungin are synergistic against Candida spp., while those of isavuconazole and amphotericin B are indifferent in vitro.

DOI10.1093/mmy/myx006
Alternate JournalMed. Mycol.
PubMed ID28204571

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