Azole resistance in Aspergillus fumigatus: Mechanisms, route of resistance selection, and clinical implications

The medical triazoles, itraconazole, voriconazole, and posaconazole, are the most widely used drugs for the management of infections caused by the saprophytic mold Aspergillus fumigatus. However, acquired azole resistance in A. fumigatus is an emerging problem that compromises the clinical efficacy of azole antifungals. Several mutations in the cyp51A gene of A. fumigatus affect the activity of all mold-active antifungal azoles. These mutations result in the complete loss of activity of a specific azole and are commonly associated with cross-resistance to other azoles. While azole resistance may emerge during antifungal therapy of individual azole-treated patients, selection of resistance can also occur in the environment. The selection for azole resistance within the environment poses an emerging global threat as mutations associated with environmental resistance have now been detected with increasing frequency in multiple European countries, Asia, the Middle East, and Africa.

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