A Jeanvoine1, S Rocchi1,2, G Reboux1,2, N Crini2, G Crini2, L Millon1,2. 1. Parasitology-Mycology Department, University Hospital, Besançon, France. 2. Chrono-Environnement UMR 6249 CNRS, Bourgogne Franche-Comté University, Besançon, France.
Abstract
AIMS: Emergence of azole-resistant Aspergillus fumigatus complicates management of Aspergillus diseases. Currently, selection pressure caused by azole fungicide use in farming is strongly suspected of creating resistance. As sawmills also use azole fungicides, we investigated the presence of azole-resistant strains in this environment and studied the relationship between azole fungicide use and development of resistance. METHODS AND RESULTS: Air (n = 200) and substrate (n = 600) samples were taken in 20 sawmills. Azole-resistant strains (Etest and EUCAST methods) were confirmed by sequencing the cyp51A gene and its promoters. Dosage of propiconazole and tebuconazole was performed by gas chromatography coupled with mass spectrometry. Twenty-four azole-resistant A. fumigatus strains were collected among 20 of the 600 substrate samples (3%). Eighty-three percent of theses strains had TR34 /L98H mutation. A significantly higher number of resistant strains was collected in sawmills using fungicide products made with propiconazole mixed with a high concentration of tebuconazole (P = 0·009). The presence of resistant strains was significantly linked to propiconazole quantities in substrates (P = 0·03). CONCLUSIONS: The outcome of azole-resistant A. fumigatus carrying TR34 /L98H mutation seems to greatly depend on the azole fungicide formulation and quantities of azole. These preliminary results are valuable to propose new approaches limiting the emergence of azole-resistant strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Azole resistance is an emerging problem in A. fumigatus and threatens clinical advances made possible by the use of azole antifungals in the treatment of Aspergillus-related diseases. Azole fungicides are also used in the wood industry, notably in sawmills, to protect wood from wood-destroying fungi. Through our study, we show that sawmills represent another professional environment affected by the presence of azole-resistant A. fumigatus strains carrying the TR34 /L98H mutation. Moreover, this study provides valuable preliminary results to propose some new approaches to limit the emergence of azole-resistant A. fumigatus strains.
AIMS: Emergence of azole-resistant Aspergillus fumigatus complicates management of Aspergillus diseases. Currently, selection pressure caused by azole fungicide use in farming is strongly suspected of creating resistance. As sawmills also use azole fungicides, we investigated the presence of azole-resistant strains in this environment and studied the relationship between azole fungicide use and development of resistance. METHODS AND RESULTS: Air (n = 200) and substrate (n = 600) samples were taken in 20 sawmills. Azole-resistant strains (Etest and EUCAST methods) were confirmed by sequencing the cyp51A gene and its promoters. Dosage of propiconazole and tebuconazole was performed by gas chromatography coupled with mass spectrometry. Twenty-four azole-resistant A. fumigatus strains were collected among 20 of the 600 substrate samples (3%). Eighty-three percent of theses strains had TR34 /L98H mutation. A significantly higher number of resistant strains was collected in sawmills using fungicide products made with propiconazole mixed with a high concentration of tebuconazole (P = 0·009). The presence of resistant strains was significantly linked to propiconazole quantities in substrates (P = 0·03). CONCLUSIONS: The outcome of azole-resistant A. fumigatus carrying TR34 /L98H mutation seems to greatly depend on the azole fungicide formulation and quantities of azole. These preliminary results are valuable to propose new approaches limiting the emergence of azole-resistant strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Azole resistance is an emerging problem in A. fumigatus and threatens clinical advances made possible by the use of azole antifungals in the treatment of Aspergillus-related diseases. Azole fungicides are also used in the wood industry, notably in sawmills, to protect wood from wood-destroying fungi. Through our study, we show that sawmills represent another professional environment affected by the presence of azole-resistant A. fumigatus strains carrying the TR34 /L98H mutation. Moreover, this study provides valuable preliminary results to propose some new approaches to limit the emergence of azole-resistant A. fumigatus strains.
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