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

P.A. Verweij, E. Snelders, G.H.J. Kema, E. Mellado, W.J.G. Melchers

    Research output: Contribution to journalArticleAcademicpeer-review

    395 Citations (Scopus)

    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
    Original languageEnglish
    Pages (from-to)789-795
    JournalThe Lancet Infectious Diseases
    Volume9
    Issue number12
    DOIs
    Publication statusPublished - 2009

    Keywords

    • 14-alpha-demethylase gene cyp51
    • invasive aspergillosis
    • in-vitro
    • penicillium-digitatum
    • demethylase gene
    • cross-resistance
    • antifungal drugs
    • itraconazole
    • sensitivity
    • mutations

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