Parasitology-Mycology Department, University Hospital, Besançon, France.
Chrono-Environnement UMR 6249 CNRS, Bourgogne Franche-Comté University, Besançon, France.
Environ Sci Pollut Res Int. 2018 Nov;25(32):32015-32023. doi: 10.1007/s11356-018-3177-6. Epub 2018 Sep 14.
Medical azole antifungals are major compounds used to prevent and to treat invasive aspergillosis (IA). Azole fungicides, called DMI (14-alpha demethylase inhibitors), are also widely used for crop protection and have been reported to be linked to azole-resistant A. fumigatus (aR-Af) development in the environment. The aim of this study was to determine whether or not market gardens that spray DMIs in Eastern France are also affected by the presence of aR-Af. Forty aR-Afs were detected in soils in only two of the four market gardens using DMIs, with 23% (7/30) and 10% (3/30) of soils containing aR-Af. A total of 87.5% of these isolates had the TR34/L98H mutation and 22.5% the TR46/Y121F/T289A mutation on the cyp51A gene. Analyses of residual azole concentrations in soils showed the presence of difenoconazole for up to 2 years after spraying, but only in soils of market gardens where aR-Af was detected. It is very important to identify professional activities that could lead to aR-Af development and to develop preventive measures for at-risk patients living near professional activities using DMIs. We have to better understand why, in some cases, the use of DMI is not linked to aR-Af. Measures should be taken to avoid the use of DMI conferring cross-resistance to preserve the efficiency of human therapeutics.
医用唑类抗真菌药物是预防和治疗侵袭性曲霉菌病(IA)的主要化合物。唑类杀真菌剂,称为 DMI(14-α 去甲基酶抑制剂),也广泛用于作物保护,并已被报道与环境中唑类抗性烟曲霉(aR-Af)的发展有关。本研究旨在确定在法国东部使用 DMI 喷洒的农贸市场是否也受到 aR-Af 的影响。仅在使用 DMI 的四个农贸市场中的两个中检测到 40 株 aR-Af,其中 23%(7/30)和 10%(3/30)的土壤含有 aR-Af。这些分离株中共有 87.5%在 cyp51A 基因上具有 TR34/L98H 突变,22.5%具有 TR46/Y121F/T289A 突变。对土壤中残留唑类浓度的分析表明,在喷洒后长达 2 年内仍存在二氟苯醚唑,但仅在检测到 aR-Af 的农贸市场土壤中存在。识别可能导致 aR-Af 发展的专业活动并为使用 DMI 的高危患者制定预防措施非常重要。我们必须更好地理解为什么在某些情况下,使用 DMI 与 aR-Af 无关。应采取措施避免使用赋予交叉耐药性的 DMI,以保留人类治疗的功效。