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Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole

The paucity of effective antifungals against Aspergillus and increasing resistance, the recognition of the importance of Aspergillus biofilm in several clinical settings, and reports of verapamil—a calcium channel blocker—efficacy against Candida biofilm and hyphal growth, and synergy with an azole...

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Autores principales: Nazik, Hasan, Choudhary, Varun, Stevens, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715943/
https://www.ncbi.nlm.nih.gov/pubmed/29371566
http://dx.doi.org/10.3390/jof3030050
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author Nazik, Hasan
Choudhary, Varun
Stevens, David A.
author_facet Nazik, Hasan
Choudhary, Varun
Stevens, David A.
author_sort Nazik, Hasan
collection PubMed
description The paucity of effective antifungals against Aspergillus and increasing resistance, the recognition of the importance of Aspergillus biofilm in several clinical settings, and reports of verapamil—a calcium channel blocker—efficacy against Candida biofilm and hyphal growth, and synergy with an azole antifungal in vitro, led to a study of verapamil ± voriconazole against Aspergillus. Broth macrodilution methodology was utilized for MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) determination. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to verapamil, verapamil plus voriconazole, or voriconazole alone. For biofilm formation, we found less inhibition from the combinations than with either drug alone, or less inhibition from the combination than that of the more potent drug alone. For preformed biofilm, we found no significant change in activity comparing voriconazole alone compared to added verapamil, and no significant alteration of activity of the more potent voriconazole, at any concentration in the range tested, by addition of a concentration of verapamil that is inhibitory alone. In full checkerboard assays with planktonic fungus, there was no indication of any effect of one drug on the other (indifference). Although verapamil was similarly inactive against planktonic Aspergillus, as with Candida, verapamil was indeed active against Aspergillus biofilm. However, indifference and antagonism was found with voriconazole.
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spelling pubmed-57159432018-01-19 Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole Nazik, Hasan Choudhary, Varun Stevens, David A. J Fungi (Basel) Article The paucity of effective antifungals against Aspergillus and increasing resistance, the recognition of the importance of Aspergillus biofilm in several clinical settings, and reports of verapamil—a calcium channel blocker—efficacy against Candida biofilm and hyphal growth, and synergy with an azole antifungal in vitro, led to a study of verapamil ± voriconazole against Aspergillus. Broth macrodilution methodology was utilized for MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) determination. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to verapamil, verapamil plus voriconazole, or voriconazole alone. For biofilm formation, we found less inhibition from the combinations than with either drug alone, or less inhibition from the combination than that of the more potent drug alone. For preformed biofilm, we found no significant change in activity comparing voriconazole alone compared to added verapamil, and no significant alteration of activity of the more potent voriconazole, at any concentration in the range tested, by addition of a concentration of verapamil that is inhibitory alone. In full checkerboard assays with planktonic fungus, there was no indication of any effect of one drug on the other (indifference). Although verapamil was similarly inactive against planktonic Aspergillus, as with Candida, verapamil was indeed active against Aspergillus biofilm. However, indifference and antagonism was found with voriconazole. MDPI 2017-09-20 /pmc/articles/PMC5715943/ /pubmed/29371566 http://dx.doi.org/10.3390/jof3030050 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nazik, Hasan
Choudhary, Varun
Stevens, David A.
Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
title Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
title_full Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
title_fullStr Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
title_full_unstemmed Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
title_short Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
title_sort verapamil inhibits aspergillus biofilm, but antagonizes voriconazole
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715943/
https://www.ncbi.nlm.nih.gov/pubmed/29371566
http://dx.doi.org/10.3390/jof3030050
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