Azole resistance in Aspergillus fumigatus: a side-eff ect of environmental fungicide use?

• Published in: The Lancet infectious diseases Vol. 9; no. 12
• Main Authors: Verweij, P.A, Snelders, E, Kema, G.H.J, Mellado, E, Melchers, W.J.G
• Format: Journal Article
• Published: 2009
• Subjects: 14-alpha-demethylase gene cyp51; antifungal drugs; cross-resistance; demethylase gene; in-vitro; invasive aspergillosis; itraconazole; mutations; penicillium-digitatum; sensitivity
• ISSN: 1473-3099; 1474-4457

Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6·0–12·8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A and a 34-bp tandem repeat in the gene-promoter region, was found in over 90% of clinical A fumigatus isolates. This is consistent with a route of resistance development through exposure to azole compounds in the environment. Indeed, TR/L98H A fumigatus isolates were cultured from soil and compost, were shown to be cross-resistant to azole fungicides, and genetically related to clinical resistant isolates. Azoles are abundantly used in the environment and the presence of A fumigatus resistant to medical triazoles is a major challenge because of the possibility of worldwide spread of resistant isolates. Reports of TR/L98H in other European countries indicate that resistance might already be spreading