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Open AccessArticle

Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole

by Hasan Nazik 1,2,*,†, Varun Choudhary 1 and David A. Stevens 1,2
California Institute for Medical Research, 2260 Clove Dr., San Jose, CA 95128, USA
Division of Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, CA 94305, USA
Author to whom correspondence should be addressed.
Permanent address: Department of Medical Microbiology, Faculty of Medicine, Istanbul University, Istanbul 34452, Turkey.
J. Fungi 2017, 3(3), 50;
Received: 10 August 2017 / Revised: 15 September 2017 / Accepted: 18 September 2017 / Published: 20 September 2017
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. View Full-Text
Keywords: verapamil; Aspergillus; biofilm; voriconazole verapamil; Aspergillus; biofilm; voriconazole
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Nazik, H.; Choudhary, V.; Stevens, D.A. Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole. J. Fungi 2017, 3, 50.

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