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葡萄牙北部临床环境中的菌种及抗真菌药敏情况:隐匿菌种与新型唑类耐药性研究

Species and Antifungals Susceptibility in Clinical Setting in the North of Portugal: Cryptic Species and Emerging Azoles Resistance in .

作者信息

Pinto Eugénia, Monteiro Carolina, Maia Marta, Faria Miguel A, Lopes Virgínia, Lameiras Catarina, Pinheiro Dolores

机构信息

Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy of University of Porto, Porto, Portugal.

Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Matosinhos, Portugal.

出版信息

Front Microbiol. 2018 Jul 23;9:1656. doi: 10.3389/fmicb.2018.01656. eCollection 2018.

DOI:10.3389/fmicb.2018.01656
PMID:30083151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6065200/
Abstract

spp. are agents of a broad-spectrum of diseases among humans. Their growing resistance to azoles, the cornerstone in the management of human aspergillosis, is a worrisome problem around the world. Considering lack of data from Portugal on this topic, particularly from the northern region, a retrospective surveillance study was planned to assess frequency of cryptic species and azoles resistance. A total of 227 clinical isolates, mainly from the respiratory tract (92.1%), collected from three hospitals serving a population of about three million people, were studied for their epidemiology and antifungal susceptibility patterns determined by the E.DEF.9.3 protocol of EUCAST. Employing molecular methods, seven complexes were identified; was the most frequent isolate (86.7%). A 7.5% prevalence of cryptic species was found; ( complex-3.1%) and (-2.2%) were the most frequent. Amongst cryptic species, it was found a percentage of resistance to voriconazole, posaconazole and isavuconazole of 47.1, 82.4, and 100%, respectively. Five showed pan-azole resistance. Sequencing their gene revealed the presence of one isolate with TR46/Y121F/T289A mutation and two isolates with TR34/L98H mutation. This study emphasizes the need to identify strains to the species level and to evaluate their antifungal susceptibility in all human originated spp. isolates, particularly those from invasive aspergillosis.

摘要

曲霉属物种是人类多种疾病的病原体。它们对作为治疗人类曲霉病基石的唑类药物的耐药性不断增强,这是一个全球范围内令人担忧的问题。鉴于葡萄牙缺乏关于这一主题的数据,特别是来自北部地区的数据,因此计划开展一项回顾性监测研究,以评估隐匿菌种的频率和唑类耐药性。对从三家医院收集的总共227株临床分离株(主要来自呼吸道,占92.1%)进行了研究,这些医院服务的人口约为300万,采用欧洲抗菌药物敏感性试验委员会(EUCAST)的E.DEF.9.3方案确定其流行病学和抗真菌药敏模式。采用分子方法,鉴定出七个复合体;烟曲霉是最常见的分离株(86.7%)。发现隐匿菌种的患病率为7.5%;烟曲霉复合群(3.1%)和黄曲霉(2.2%)是最常见的。在隐匿菌种中,发现对伏立康唑、泊沙康唑和艾沙康唑的耐药率分别为47.1%、82.4%和100%。有五株烟曲霉显示对所有唑类药物耐药。对它们的cyp51基因进行测序,发现一株分离株存在TR46/Y121F/T289A突变,两株分离株存在TR34/L98H突变。本研究强调有必要将菌株鉴定到种水平,并评估所有源自人类的曲霉属物种分离株,特别是那些来自侵袭性曲霉病的分离株的抗真菌药敏性。

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本文引用的文献

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First description of clinical Aspergillus fumigatus cyp51A TR/Y121F/T289A mutant in Portugal.葡萄牙首次对临床烟曲霉cyp51A TR/Y121F/T289A突变体的描述。
J Glob Antimicrob Resist. 2018 Jun;13:190-191. doi: 10.1016/j.jgar.2018.04.016. Epub 2018 May 7.
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Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.曲霉病的诊断和治疗:2017 年 ESCMID-ECMM-ERS 指南执行摘要。
Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38. doi: 10.1016/j.cmi.2018.01.002. Epub 2018 Mar 12.
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Isavuconazole susceptibility of clinical Aspergillus fumigatus isolates and feasibility of isavuconazole dose escalation to treat isolates with elevated MICs.临床烟曲霉分离株的伊曲康唑药敏性和升高 MIC 分离株采用伊曲康唑剂量递增治疗的可行性。
J Antimicrob Chemother. 2018 Jan 1;73(1):134-142. doi: 10.1093/jac/dkx354.
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Evaluation of the in vitro activity of isavuconazole and comparator voriconazole against 2635 contemporary clinical Candida and Aspergillus isolates.评估伊曲康唑和比较剂伏立康唑对 2635 株当代临床念珠菌和曲霉菌分离株的体外活性。
Clin Microbiol Infect. 2017 Nov;23(11):882-887. doi: 10.1016/j.cmi.2017.03.023. Epub 2017 Apr 1.
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Triazole Resistance in Aspergillus Species: An Emerging Problem.三唑类耐药的曲霉菌属:一个新出现的问题。
Drugs. 2017 Apr;77(6):599-613. doi: 10.1007/s40265-017-0714-4.
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Clinical implications of globally emerging azole resistance in Aspergillus fumigatus.烟曲霉全球范围内新出现的唑类耐药性的临床意义
Philos Trans R Soc Lond B Biol Sci. 2016 Dec 5;371(1709). doi: 10.1098/rstb.2015.0460.
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Evaluation of MIC Strip Isavuconazole Test for Susceptibility Testing of Wild-Type and Non-Wild-Type Aspergillus fumigatus Isolates.用于野生型和非野生型烟曲霉分离株药敏试验的MIC条伊曲康唑试验评估
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