Summary auto-generated
Researchers evaluated the effectiveness of voriconazole (VRC) and fluconazole (FLC) against 295 Candida isolates from 189 patients using adapted NCCLS methodology. The study included multiple Candida species, with C. albicans being the most common. Minimum inhibitory concentrations (MICs) showed that VRC was generally one log unit more potent than FLC. Among 42 isolates with reduced FLC susceptibility, 83.3% demonstrated low VRC MICs below 2 μg/L, including most FLC-resistant species like C. glabrata and C. krusei. Notably, 60% of deep-seated infections caused by FLC-resistant Candida showed low VRC MICs. While some cross-resistance between azoles was observed, VRC exhibited activity against FLC-resistant isolates and less common Candida species. The study concludes that voriconazole's favorable pharmacokinetics and proportionally increased potency make it a viable therapeutic option for empirical treatment of severe candida infections, particularly when fluconazole resistance is present or suspected.
Key findings
- Voriconazole MICs were approximately 1 log unit lower than fluconazole MICs across Candida species, indicating greater potency
- Among 42 fluconazole-resistant isolates, 83.3% showed low voriconazole MICs (<2 μg/L), including 95% of C. glabrata and 100% of C. krusei
- Voriconazole demonstrated activity against 60% of deep-seated infections caused by fluconazole-resistant Candida isolates
- Proportional cross-resistance was observed, with fluconazole-resistant isolates showing higher voriconazole MICs than susceptible isolates, but remaining treatable at achievable serum levels
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Abstract
An adapted NCCLS M27-A method was used to evaluate the activity of voriconazole (VRC) and fluconazole (FLC) against 295 Candida isolates collected from 189 patients (including isolates from deep sites). Isolates included 186 C. albicans, 54 C. glabrata, 27 C. tropicalis, 14 C. parapsilosis, 6 C. krusei, 6 C. lusitaniae, 1 C. lypolytica and 1 C. sake. Forty-two isolates had reduced susceptibility to FLC (MIC >8 mg/L); 83.3% of these had VRC MICs 2 mg/L (9 of 11 C. albicans, 18 of 19 C. glabrata, 6 of 6 C. krusei, 2 of 2 C. lusitaniae and 0 of 4 C. tropicalis), including 60% of isolates collected from deep-seated infections. These results suggested that in the era of azole resistance, VRC has a promising antifungal activity for serious infections with Candida spp., including most species with low susceptibility to FLC and uncommonly isolated species.