Résistance aux azolés chez Aspergillus

Among Aspergillus species, Aspergillus fumigatus is responsible for various pulmonary diseases ranging from chronic and/or immuno-allergic forms in immunocompetent host, to severe invasive aspergillosis (IA) in immunocompromised patient. Triazole antifungals are the mainstay of therapy for aspergillosis, as first-line treatment for IA (voriconazole), or for prophylaxis. Over the past decade, the emergence of clinical and environmental azole-resistant A. fumigatus isolates has been reported in Europe, threatening the azole effectiveness for treatment of aspergillosis. The main mechanism of resistance is the occurrence of mutations in cyp51A gene, encoding the azole target enzyme (14 α-demethylase). Two hypothesis for azole resistance emergence are debated: azole resistance following long periods of azole treatment in the clinical setting, and an environmental origin related to the extended use of azole fungicides in agriculture. Thus, a reliable screening of resistant isolates is required in laboratories to improve the clinical management of IA patients with resistant strain, at high risk of treatment failure. Here, we successively review the current epidemiology, molecular mechanisms and clinical implication of Aspergillus azole resistance.