Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Radboudumc-CWZ Centre of Expertise for Mycology, Nijmegen, the Netherlands.
J Infect Chemother. 2021 Dec;27(12):1774-1778. doi: 10.1016/j.jiac.2021.08.024. Epub 2021 Sep 10.
Prevalence reports of triazole-resistance in Aspergillus fumigatus differ between countries and centers and may likewise vary over time. Continuous local surveillance programs to establish the evolving epidemiology of triazole-resistance in A. fumigatus are crucial to guide therapeutic recommendations. Here, we determined the prevalence of triazole-resistance in A. fumigatus complex culture-positive patients at the tertiary care center University Hospitals Leuven in Belgium in clinical isolates from 2016 to 2020.
All A. fumigatus complex isolates cultured from UZ Leuven patients between 2016 and 2020 were screened for triazole-resistance. Confirmation of resistance to voriconazole, posaconazole and itraconazole was performed with the European Committee for Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. Mutations in the cyp51A gene in triazole-resistant isolates were determined by sequencing. Patients were classified as susceptible or resistant cases based on their isolate's susceptibility phenotype.
We screened 2494 A. fumigatus complex isolates from 1600 patients (320 ± 38 [SD] patients per year). The prevalence of triazole-resistance in patients was 8.3% (28/337), 6.7% (26/386), 7.0% (21/301), 7.1% (21/294) and 7.4% (21/282) in 2016, 2017, 2018, 2019 and 2020 respectively, with an overall triazole-resistance prevalence of 7.1% (85/1192; 95% CI 6.6-7.7%). The TR/L98H mutation was the most prevalent (83.0%, 78/94) with most isolates displaying resistance to all triazole antifungals tested (94.8%, 74/78).
The prevalence of triazole-resistance in A. fumigatus has remained stable from 2016 to 2020 in our center ranging between 6.7 and 8.3%, with an overall five-year prevalence of 7.1%. The environmentally associated cyp51A gene mutations were most prevalent amongst triazole-resistant isolates and conferred resistance to all antifungals tested in 73% of the isolates.
烟曲霉中三唑耐药性的流行率报告在不同国家和中心之间存在差异，并且随着时间的推移也可能有所不同。建立烟曲霉中三唑耐药性演变的流行病学的连续本地监测计划对于指导治疗建议至关重要。在这里，我们在比利时鲁汶大学医院的三级保健中心确定了 2016 年至 2020 年临床分离物中烟曲霉复合体培养阳性患者中三唑耐药性的流行率。
从 2016 年至 2020 年培养的所有烟曲霉复合体分离物均进行了三唑耐药性筛查。使用欧洲抗菌药物敏感性测试委员会（EUCAST）肉汤微量稀释法对伏立康唑、泊沙康唑和伊曲康唑的耐药性进行了确认。通过测序确定三唑耐药分离物中 cyp51A 基因的突变。根据分离物的药敏表型，将患者分为敏感或耐药病例。
我们从 1600 名患者中筛选了 2494 株烟曲霉复合体分离株（每年 320 ± 38 [SD]名患者）。患者中三唑耐药率分别为 2016 年 8.3%（28/337）、2017 年 6.7%（26/386）、2018 年 7.0%（21/301）、2019 年 7.1%（21/294）和 2020 年 7.4%（21/282），总体三唑耐药率为 7.1%（85/1192；95%CI 6.6-7.7%）。TR/L98H 突变最为常见（83.0%，78/94），大多数分离物对所有测试的三唑类抗真菌药物均显示耐药（94.8%，74/78）。
在我们的中心，从 2016 年到 2020 年，烟曲霉中三唑耐药率保持稳定，范围在 6.7%到 8.3%之间，总五年的耐药率为 7.1%。环境相关的 cyp51A 基因突变在三唑耐药分离物中最为常见，在 73%的分离物中对所有测试的抗真菌药物均有耐药性。
