Voriconazole -- better chances for patients with invasive mycoses

Abstract

The past two decades have witnessed an increase in serious fungal infections, without corresponding growth in available antifungal agents. Voriconazole (VRC) is a novel triazole antifungal, recently approved in Europe for treatment of serious infections caused by Aspergillus, Fusarium, Scedosporium, and resistant Candida species. Voriconazole has in vitro activity against yeasts and yeast-like fungi similar, or superior to, fluconazole (FLC), itraconazole (ITC) and amphotericin B (AMB). Candida albicans is generally the most susceptible yeast (VRC MIC subset90 of 0.06 microg/ml); C. krusei often has low MICs even in the face of FLU/ITC resistance. Voriconazole has demonstrated comparable, or better, in vitro activity than ITC and AMB against Aspergillus (mean MICs 0.19-0.58 microg/ml), Ascomycetes, Bipolaris, Fusarium, Blastomyces dermatitidis, Coccidioides immitis, dermatophytes, Histoplasma capsulatum, Malassezia, and Scedosporium angiospermum (P. boydii). The drug possesses potent fungicidal activity against moulds including Aspergillus, Scedosporium, and Fusarium. Fungicidal activity is likely due to the high affinity of VRC for fungal 14-alpha-demethylase, a concept supported by ultrastructural and biochemical analysis. Animal studies confirmed the activity of VRC against infections including pulmonary and invasive aspergillosis (IA); A. fumigatus endocarditis; fusariosis; pulmonary cryptococcosis; and invasive candidiasis. Most importantly, well-designed human clinical trials have confirmed the efficacy of VRC in the treatment of candidal esophagitis, IA, and febrile neutropenia. Smaller studies and case reports have shown VRC is useful for salvage therapy of IA, cerebral aspergillosis, Scedosporium, and other fungal infections. Clinical testing has shown VRC is safe and well tolerated; the most common side effect is benign, self-limited visual disturbance.