azoleresistant

Azole resistance, or azole-resistant fungi, describes reduced susceptibility to azole antifungals such as fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. Azoles are key first-line therapies for many fungal infections, especially those caused by Candida and Aspergillus species.

Resistance arises through multiple mechanisms. Common genetic changes include mutations or overexpression of ERG11 (CYP51A in molds), reducing drug binding; upregulation of efflux pumps (CDR and MDR families) that lower intracellular drug concentrations; and alterations in ergosterol biosynthesis. In Aspergillus fumigatus, cyp51A promoter and coding mutations such as TR34/L98H and TR46/Y121F/T289A are well described and often accompany environmental azole exposure. In Candida species, overexpression of efflux pumps and changes in ERG11 contribute to decreased susceptibility; biofilm formation also reduces drug access.

Azole resistance has been reported in several species, notably Candida albicans, Candida glabrata, Candida tropicalis, and Aspergillus fumigatus. Rates vary by geography and species and tend to be higher where azoles are widely used in medicine or agriculture. Resistance can lead to treatment failure and worse outcomes, particularly in invasive infections.

Detection relies on antifungal susceptibility testing using broth microdilution or standardized methods (CLSI or EUCAST); molecular tests can identify common resistance mutations. Management includes adjusting therapy based on results, such as switching to an effective agent (e.g., an echinocandin or liposomal amphotericin B for resistant Candida; using a non-azole or amphotericin B for Aspergillus when needed), and implementing antifungal stewardship to limit spread and environmental selection.