The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant A. fumigatus strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of cyp51 genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates.

中文翻译：

---

用于检测和推导曲霉属物种的唑类抗真菌药物耐药表型的分子工具[综述]

在过去的几年中，曲霉种中对唑类的抗药性增加了，最重要的是烟曲霉。这部分归因于仅少数抗性等位基因在环境中的全球传播。继发耐药性是一个重大的临床关注点，因为已经很难治疗具有药物敏感性菌株的侵袭性曲霉病，并且在高危患者的预防或一线治疗侵袭性曲霉病中排除以吡咯为基础的抗真菌药会极大地限制药物的选择，因此增加了免疫受损患者的死亡率。耐唑类烟曲霉引起的侵袭性曲霉病的管理选择最近，一个国际专家小组对这些菌株进行了重新评估，得出的结论是，当打算进行抗真菌治疗时，对培养分离株的耐药性测试非常重要。在环境中对唑类耐药菌株普遍流行的地理区域中，应以此类分析为指导进行初始治疗。因此，如果要在合理的基础上实施此类措施，则需要进行更多的环境和临床筛查研究，以生成当地的流行病学数据。在这里，我们提出了一个用于评估筛选研究分离株的第一个工作流程，并且我们对与cyp51基因产物中的各个氨基酸取代相关的MIC值进行了汇编，以解释DNA测序数据，特别是在没有培养分离株的情况下。