| 宁波市耐多药肺结核二线抗结核药物耐药状况及耐药基因突变特征研究 |
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| 引用本文： | 车洋,贺天锋,林律,平国华. 宁波市耐多药肺结核二线抗结核药物耐药状况及耐药基因突变特征研究[J]. 疾病监测, 2021, 36(10): 1075-1080. DOI: 10.3784/jbjc.202103100114 |
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| 作者姓名： | 车洋 贺天锋 林律 平国华 |
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| 作者单位： | 浙江省宁波市疾病预防控制中心结核病防制所,浙江宁波315010 |
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| 基金项目： | 宁波市自然科学基金（No. 2019A610385）；宁波市医疗卫生品牌学科（No. PPXK2018-10） |
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| 摘 要： | 目的 分析宁波地区耐多药肺结核（MDR-TB）二线抗结核药物耐药状况及耐药基因突变特征。 方法 研究纳入本地区2018 — 2019 年结核病耐药监测收集的1597株结核分枝杆菌痰培养阳性菌株中的133株MDR-TB作为研究对象（老年组31例，中青年组102例），应用RD105缺失基因检测法对133株MDR-TB菌株进行北京基因型鉴定，同时采用1%比例法对其进行卡那霉素、阿米卡星、卷曲霉素、氧氟沙星、左氧氟沙星5种二线抗结核药物的耐药检测。通过PCR DNA直接测序法检测6个二线抗结核药物耐药相关基因（rrs、tlyA、eis、gidB、gyrA、gyrB ）的突变特征。 结果 本地区结核分枝杆菌总的耐多药率为8.33%（133/1597），133例MDR-TB的卡那霉素、阿米卡星、卷曲霉素、氧氟沙星和左氧氟沙星的耐药率分别为7.52%（10/133）、6.01%（8/133）、3.01%（4/133）、30.08%，（40/133）、29.32%（39/133）。 133例MDR-TB 的准广泛耐药率（Pre-XDR）为28.57%（38/133）、广泛耐药率（XDR-TB）为6.01%，（8/133）。 133例MDR-TB rrs突变率为6.77%（9/133）、tlyA为7.52%（10/133）、eis为1.50%（2/133）、gidB为3.76%（5/133）、gyrA为34.59%（46/133）、gyrB为3.01%（4/133）。 6个基因的突变类型（rrs 2种、tlyA 1种、eis 2种、gidB 2种，gyrA 5种、gyrB 4种）均以点突变为主。 结论 宁波地区MDR-TB二线抗结核药物耐药形势较为严峻，尤其是氟喹诺酮类药物耐药率较高，需进一步加强耐二线抗结核药物MDR-TB的防控工作。
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| 关 键 词： | 耐药 细菌 结核分枝杆菌 基因突变 |
| 收稿时间： | 2021-03-10 |
Characteristics of second-line anti-tuberculosis drug resistance and gene mutation of multidrug-resistant Mycobacterium tuberculosis in Ningbo |
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| Affiliation: | Ningbo Prefectural Center for Disease Control and Prevention, Ningbo 315010, Zhejiang, China |
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| Abstract: | Objective To analyze the characteristics of second-line anti-tuberculosis (TB) drugs resistance and gene mutation of multidrug-resistant (MDR) Mycobacterium tuberculosis isolated in Ningbo. Methods In 1597 M. tuberculosis isolates collected in the first drug resistance survey in Ningbo between 2018 and 2019, 133 MDR isolates, including 31 isolated from elderly group and 102 isolated from young and middle age group, were used in the study. All the isolates were detected using RD105 deletion-targeted multiplex PCR for Beijing genotype identification. Gene sequencing with PCR was conducted to detect the mutations of rrs, tlyA, eis, gidB, gyrA and gyrB genes. The conventional drug susceptibility test was used to detect the resistances to 5 second-line anti TB drugs (kanamycin, amikacin, capreomycin, ofloxacin, levofloxacin). Results The multidrug resistance rate of M. tuberculosis isolates was 8.33% (133/1597) in Ningbo. The resistance rates of 133 MDR M. tuberculosis isolates to kanamycin, amikacin, capreomycin, ofloxacin and levofloxacin were 7.52% (10/133), 6.01% (8/133), 3.01% (4/133), 30.08% (40/133) and 29.32% (39/133). The rates of Pre-XDR and XDR of 133 MDR M. tuberculosis isolates were 28.57% (38/133) and 6.01% (8/133). The gene mutation rates of rrs, tlyA, eis, gidB, gyrA and gyrB of 133 MDR M. tuberculosis isolates were 6.77% (9/133), 7.52% (10/133), 1.50% (2/133), 3.76% (5/133), 34.59% (46/133) and 3.01% (4/133). There were 2 rrs mutations, 1 tlyA mutation, 2 eis mutations, 2 gidB mutations, 5 gyrA mutations and 4 gyrB mutations. Single base substitution was the main type. Conclusion The resistance of MDR M. tuberculosis to second-line anti-TB drugs was serious in Ningbo, especially the resistance to fluoroquinolone. It is necessary to strengthen the prevention and control of second-line anti TB drugs resistances of MDR M. tuberculosis. |
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