title: Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?
abstract: 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.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. p.verweij@mmb.umcn.nl
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
authors.forename: Eveline
authors.initials: E
authors.lastname: Snelders
authors.forename: Gert H J
authors.initials: GH
authors.lastname: Kema
authors.forename: Emilia
authors.initials: E
authors.lastname: Mellado
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D005060:Europe; D005656:Fungal Proteins / Q000235:genetics; D005659:Fungicides, Industrial / Q000009:adverse effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012988:Soil Microbiology; D014230:Triazoles / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D014230:Triazoles; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus