中华皮肤科杂志 ›› 2022, Vol. 55 ›› Issue (4): 316-320.doi: 10.35541/cjd.20210646

• 论著 • 上一篇    下一篇

南京某医院201株烟曲霉感染患者临床资料与唑类耐药情况回顾性分析

陈玉萍1    郑海林1    张之烽2    梅嬛1    刘维达1    刘沐桑1   

  1. 1中国医学科学院、北京协和医学院皮肤病医院真菌科，南京  210042；2南京大学医学院附属鼓楼医院检验科，南京  210008
  • 收稿日期:2021-09-06 修回日期:2022-01-05 发布日期:2022-04-01
  • 通讯作者: 刘沐桑 E-mail:liums@pumcderm.cams.cn
  • 基金资助:
    国家自然科学基金青年基金（81501726）；江苏省自然科学基金（BK20150069）；中国医学科学院中央级公益性科研院所基本科研业务费临床与转化医学研究基金项目（2019XK320077）

Retrospective analysis of 201 clinical isolates of Aspergillus fumigatus from a hospital in Nanjing: clinical characteristics of infected patients and azole resistance

Chen Yuping1, Zheng Hailin1, Zhang Zhifeng2, Mei Huan1, Liu Weida1, Liu Musang1   

  1. 1Department of Mycology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; 2Department of Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
  • Received:2021-09-06 Revised:2022-01-05 Published:2022-04-01
  • Contact: Liu Musang E-mail:liums@pumcderm.cams.cn
  • Supported by:
    National Natural Science Foundation of China （81501726）; Natural Science Foundation of Jiangsu Province of China （BK20150069）; The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences  （2019XK320077）

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摘要： 【摘要】 目的 总结南京某医院烟曲霉感染患者的临床特征，初步评估烟曲霉临床分离株的唑类耐药情况，以及唑类耐药烟曲霉出现的高危因素。方法 收集2017年3月至2021年2月南京市鼓楼医院检验科自住院患者中分离到的烟曲霉菌株，分析感染患者的临床资料，并对分离的烟曲霉进行唑类药物敏感性试验和cyp51A基因及其启动子区的突变检测。结果 共收集烟曲霉201株，主要来自痰标本，感染患者中，男131例，女70例，年龄（64.2 ± 15.8）岁，主要分布在呼吸内科（79例）、重症医学科（34例）、风湿免疫科（19例）等；患者常见基础疾病有间质性肺炎（32例）、恶性肿瘤（18例）、肺炎（13例）、外伤（12例）以及系统性红斑狼疮（8例）等。药物敏感性试验显示，6株（2.99%）烟曲霉对伊曲康唑和泊沙康唑耐药，3例感染唑类耐药烟曲霉的患者在送检前使用过抗真菌药。对6株唑类耐药烟曲霉的cyp51A基因及其启动子区进行测序，发现其中5株携带TR34/L98H/S297T/F495I位点突变，另1株携带TR34/L98H突变。结论 与既往报道的2010—2015年中国烟曲霉临床株唑类耐药数据相比，2017—2021年南京市鼓楼医院烟曲霉对唑类的耐药水平并未升高，耐药机制多为cyp51A基因及其启动子区TR34/L98H/S297T/F495I突变。

关键词: 烟曲霉菌, 分子流行病学, 微生物敏感性试验, 抗药性, 真菌, DNA突变分析, 基础疾病

Abstract: 【Abstract】 Objective To summarize clinical characteristics of patients with Aspergillus fumigatus infection in a hospital in Nanjing, to preliminarily assess azole resistance in clinical isolates of Aspergillus fumigatus, and to investigate risk factors for the emergence of azole-resistant Aspergillus fumigatus. Methods Clinical isolates of Aspergillus fumigatus were collected from inpatients in Department of Laboratory, Nanjing Drum Tower Hospital from March 2017 to February 2021. Clinical data on these infected patients were analyzed, azole sensitivity testing and mutation analysis of the cyp51A gene and its promoter region were performed for these Aspergillus fumigatus isolates. Results A total of 201 strains of Aspergillus fumigatus were collected, and mainly isolated from sputum specimens. Among the infected patients, there were 131 males and 70 females, and their age were 64.2 ± 15.8 years. The patients were mainly collected from department of respiratory medicine （79 cases） , department of intensive medicine （34 cases）, department of rheumatology （19 cases）, etc. Among these patients, common underlying diseases included interstitial pneumonia （32 cases）, malignant tumors （18 cases）, pneumonia （13 cases）, trauma （12 cases） , systemic lupus erythematosus （8 cases）, etc. Drug susceptibility testing showed that 6 （2.99%） strains of Aspergillus fumigatus were resistant to itraconazole and posaconazole, and 3 patients infected with azole-resistant Aspergillus fumigatus had used antifungal drugs before testing. Sequencing was performed on the cyp51A gene and its promoter region in the 6 strains of azole-resistant Aspergillus fumigatus, and showed TR34/L98H/S297T/F495I mutation in 5 strains and TR34/L98H mutation in 1 strain. Conclusion Compared with previously published data about azole resistance in China during 2010 -2015, the resistance of Aspergillus fumigatus to azoles in Nanjing Drum Tower Hospital did not increase from 2017 to 2021, and the mechanism of azole resistance was mostly associated with TR34/L98H/S297T/F495I mutation in the cyp51A gene and its promoter region.

Key words: Aspergillus fumigatus, Molecular epidemiology, Microbial sensitivity tests, Drug resistance, fungal, DNA mutational analysis, Underlying diseases