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用于检测和推断曲霉属物种中唑类抗真菌药物耐药表型的分子工具

Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.

作者信息

Dudakova Anna, Spiess Birgit, Tangwattanachuleeporn Marut, Sasse Christoph, Buchheidt Dieter, Weig Michael, Groß Uwe, Bader Oliver

机构信息

Institute for Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany.

3rd Department of Internal Medicine, Hematology and Oncology, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany.

出版信息

Clin Microbiol Rev. 2017 Oct;30(4):1065-1091. doi: 10.1128/CMR.00095-16.

DOI:10.1128/CMR.00095-16
PMID:28903985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5608879/
Abstract

The incidence of azole resistance in species has increased over the past years, most importantly for . 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 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 genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates.

摘要

在过去几年中,该菌种中唑类耐药的发生率有所上升,对于[具体菌种名称]而言尤为重要。这部分归因于仅少数耐药等位基因在环境中的全球传播。继发性耐药是一个重大的临床问题,因为侵袭性曲霉病对药物敏感菌株的治疗本就困难,而在高危患者中,预防或一线治疗侵袭性曲霉病时排除基于唑类的抗真菌药物将极大地限制药物选择,从而增加免疫受损患者的死亡率。一个国际专家小组最近重新评估了由唑类耐药[具体菌种名称]菌株引起的侵袭性曲霉病的管理方案,得出结论:当打算进行抗真菌治疗时,对培养的分离株进行耐药性检测非常必要。在唑类耐药菌株环境流行率高的地理区域,初始治疗应以此类分析为指导。因此,如果要在合理的基础上实施此类措施,就需要更多的环境和临床筛查研究来生成当地的流行病学数据。在此,我们提出了第一个用于评估筛查研究中分离株的工作流程,并汇总了与[具体基因名称]基因产物中单个氨基酸取代相关的最低抑菌浓度(MIC)值,以解释DNA测序数据,特别是在没有培养分离株的情况下。

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本文引用的文献

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A Novel Environmental Azole Resistance Mutation in and a Possible Role of Sexual Reproduction in Its Emergence.一种新型的环境唑类抗性突变以及有性生殖在其出现过程中的可能作用。
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Culture-Based Methods and Molecular Tools for Azole-Resistant Aspergillus fumigatus Detection in a Belgian University Hospital.比利时某大学医院中用于检测耐唑类烟曲霉的基于培养的方法和分子工具
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A new time-dependent approach for assessment of the impact of invasive aspergillosis shows effect on short- but not on long-term survival of patients with AML or high-risk MDS.一种用于评估侵袭性曲霉病影响的新的时间依赖性方法显示,其对急性髓系白血病(AML)或高危骨髓增生异常综合征(MDS)患者的短期生存有影响,但对长期生存无影响。
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