Τίτλος:
In vitro combination therapy with isavuconazole against Candida spp.
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 timekill 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 %ΔE value) with the highest synergy occurring against C. albicans (Σ SYN% = 8.8%-110%). Time-kill assays showed that the isavuconazole-micafungin combination demonstrated concentrationdepended 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 andmicafungin are synergistic against Candida spp., while those of isavuconazole and amphotericin B are indifferent in vitro. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved.
Συγγραφείς:
Katragkou, 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.
Περιοδικό:
Medical Mycology
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
amphotericin B deoxycholate; isavuconazole; micafungin; polyene; amphotericin B; antifungal agent; echinocandin; isavuconazole; lipopeptide; nitrile; pyridine derivative; triazole derivative, antifungal activity; Article; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; controlled study; drug potentiation; in vitro study; invasive candidiasis; minimum inhibitory concentration; nonhuman; Pichia kudriavzevii; Candida; drug effect; drug potentiation; invasive candidiasis; microbial sensitivity test; time factor, Amphotericin B; Antifungal Agents; Candida; Candidiasis, Invasive; Drug Synergism; Echinocandins; In Vitro Techniques; Lipopeptides; Microbial Sensitivity Tests; Nitriles; Pyridines; Time Factors; Triazoles
