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

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

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。

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.