2013-2017年湖南省耒阳市结核分枝杆菌耐药性特征的动态研究

贺文从 谭云洪 梁伟民 包晶晶 宋怡蒙 刘东鑫 刘春法 赵雁林

贺文从, 谭云洪, 梁伟民, 包晶晶, 宋怡蒙, 刘东鑫, 刘春法, 赵雁林. 2013-2017年湖南省耒阳市结核分枝杆菌耐药性特征的动态研究[J]. 疾病监测, 2020, 35(4): 350-356. doi: 10.3784/j.issn.1003-9961.2020.04.016
引用本文: 贺文从, 谭云洪, 梁伟民, 包晶晶, 宋怡蒙, 刘东鑫, 刘春法, 赵雁林. 2013-2017年湖南省耒阳市结核分枝杆菌耐药性特征的动态研究[J]. 疾病监测, 2020, 35(4): 350-356. doi: 10.3784/j.issn.1003-9961.2020.04.016
Wencong He, Yunhong Tan, Weimin Liang, Jingjing Bao, Yimeng Song, Dongxin Liu, Chunfa Liu, Yanlin Zhao. Dynamic characteristics of drug resistant tuberculosis in Leiyang, Hunan, 2013–2017[J]. Disease Surveillance, 2020, 35(4): 350-356. doi: 10.3784/j.issn.1003-9961.2020.04.016
Citation: Wencong He, Yunhong Tan, Weimin Liang, Jingjing Bao, Yimeng Song, Dongxin Liu, Chunfa Liu, Yanlin Zhao. Dynamic characteristics of drug resistant tuberculosis in Leiyang, Hunan, 2013–2017[J]. Disease Surveillance, 2020, 35(4): 350-356. doi: 10.3784/j.issn.1003-9961.2020.04.016

2013-2017年湖南省耒阳市结核分枝杆菌耐药性特征的动态研究

doi: 10.3784/j.issn.1003-9961.2020.04.016
基金项目: 国家科技重大专项(No. 2018ZX10103001)
详细信息
    作者简介:

    贺文从,女,山东省莱芜市人,硕士研究生在读,主要从事结核病分子流行病学研究,Email:hewc2312@163.com

    通讯作者:

    赵雁林,Te:010–58900777,Email:zhaoyl@chinacdc.cn

  • 中图分类号: R52

Dynamic characteristics of drug resistant tuberculosis in Leiyang, Hunan, 2013–2017

Funds: The National Science and Technology Major Project (No. 2018ZX10103001)
More Information
  • 摘要: 目的分析2013 — 2017年湖南省耒阳市结核分枝杆菌的耐药性动态变化趋势,了解该地区流行结核分枝杆菌耐药谱特征,为结核病的化疗方案制定和防控提供科学参考依据。方法回顾性分析2013 — 2017年耒阳市收集的国家耐药监测菌株,经基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)鉴定为结核分枝杆菌的菌株采用微孔板法测定8种常用一线二线抗结核药的最小抑菌浓度,采用统计描述和趋势χ2检验分析其耐药特征变化。结果本研究共纳入568株结核分枝杆菌临床分离株,其中105(18.49%)株来自复治结核病患者,463(81.51%)株来自初治结核病患者。 总耐药率为22.13%(120/568),总耐多药率为6.34%(36/568),广泛耐药结核率为0.35%(2/568)。 耐药趋势分析结果显示,仅对氟喹诺酮类药物的耐药率呈逐年升高趋势(趋势χ2=8.585,P=0.003),对其他药物的耐药率、总耐药率、耐多药率等变化不大,差异无统计学意义。结论湖南省耒阳市结核病耐药情况较严重,氟喹诺酮类耐药率在5年间呈逐年上升趋势,提示需要提高警觉,加强氟喹诺酮类药物的规范化使用;在耐药结核病患者治疗中需充分考虑其交叉耐药情况,同时加强该地区耐多药结核病患者的管理以减少原发性耐药结核病的产生。
  • 图  1  2013-2017年氧氟沙星和莫西沙星耐药率拟合线性回归模型

    注:OFL. 氧氟沙星;MXF. 莫西沙星

    Figure  1.  Fitting linear regression model of ofloxacin and moxifloxacin resistance rates from 2013 to 2017

    图  2  568株结核分枝杆菌的耐药相关矩阵

    注:方格里数值表示相关系数,取值范围为[−1,1],正值表示正相关,负值表示负相关,绝对值大小指示相关性强弱,绝对值越大,两变量的相关性越强,0.8~1为极强相关,0.6~0.8为强相关,0.4~0.6为中度相关,0.2~0.4为弱相关,0~0.2为极弱相关或无关,经检验表格里的相关系数均有统计学意义(P<0.05);INH. 异烟肼;RIF. 利福平;EMB. 乙胺丁醇;SM. 链霉素;OFL. 氧氟沙星;MXF. 莫西沙星;AMI. 阿米卡星;KAN. 卡那霉素

    Figure  2.  Correlation matrix of drug resistances of 568 M. tuberculosis strains

    图  3  568株结核分枝杆菌的最小抑菌浓度分布

    注:虚线为CLSI推荐的判定药敏结果的临界浓度值;R. 耐药;S. 敏感

    Figure  3.  Minimum inhibitory concentration distributions of 568 M. tuberculosis strains

    表  1  药物浓度范围和临界浓度值

    Table  1.   Concentration range and critical concentration of drugs

     药物浓度范围(μg/ml)临界浓度(μg/ml)
    异烟肼0.03~4.00 0.20
    利福平0.12~16.001.00
    乙胺丁醇0.50~32.005.00
    链霉素0.25~32.002.00
    氧氟沙星0.25~32.002.00
    莫西沙星0.06~8.00 0.50
    阿米卡星0.12~16.004.00
    卡那霉素0.60~40.005.00
    下载: 导出CSV

    表  2  568例结核病患者的基本人口学信息

    Table  2.   Demographic information of 568 patients with tuberculosis

     分组病例数(例)构成比(%)
    性别
     男性45079.23
     女性11820.77
    年龄组(岁)
      0~ 8214.44
     30~10017.60
     45~21036.97
     60~17630.99
    居住地
     农村44277.82
     城镇12622.18
    职业
     农民46080.99
     其他10819.01
    文化程度
     文盲或半文盲10217.96
     小学或初中40170.60
     高中及以上 6511.44
    初复治分类
     复治10518.49
     初治46381.51
    下载: 导出CSV

    表  3  568株结核分枝杆菌对一线抗结核药耐药情况

    Table  3.   Drug resistances of 568 M. tuberculosis strains to first-line anti-TB drugs

     耐药类型初治患者分离株(n=463)复治患者分离株(n=105)合计(n=568)χ2P
    菌株数(株)耐药率(%)菌株数(株)耐药率(%)菌株数(株)耐药率(%)
    任意耐药6814.693432.3810217.96 18.188<0.001
     INH5311.452321.90 7613.38 8.076 0.004
     RIF26 5.622220.95 48 8.45 26.022<0.001
     EMB13 2.81 6 5.71 19 3.35 1.428 0.232
     SM36 7.781615.24 52 9.15 5.731 0.017
    单耐药37 7.991514.29 52 9.15 4.077 0.043
     INH22 4.75 8 7.62 30 5.28 1.407 0.236
     RIF 4 0.86 4 3.81 8 1.41 3.437 0.064
     EMB 0 0.00 0 0.00 0 0.00
     SM11 2.38 3 2.86 14 2.46<0.001>0.999
    耐多药22 4.751413.33 36 6.34 10.618 0.001
     INH+RIF 4 0.86 5 4.76 9 1.58 6.027 0.014
     INH+RIF+EMB 2 0.43 1 0.95 3 0.53 0.459a
     INH+RIF+SM 6 1.30 4 3.81 10 1.76 1.842 0.175
     INH+RIF+EMB+SM10 2.16 4 3.81 14 2.46 0.404 0.525
    多耐药 9 1.94 5 4.76 14 2.46 1.777 0.183
     INH+SM 8 1.73 1 0.95 9 1.58 0.020 0.887
     RIF+SM 0 0.00 3 2.86 3 0.53 0.006a
     INH+EMB+SM 1 0.22 0 0.00 1 0.18 >0.999a
     RIF+EMB+SM 0 0.00 1 0.95 1 0.18 0.185a
      注:INH. 异烟肼;RIF. 利福平;EMB. 乙胺丁醇;SM. 链霉素;a. 由Fisher确切概率法计算;−. 无法计算;任意耐药指经体外药敏试验证实结核分枝杆菌对指定的抗结核药物耐药,而不考虑对其他药物是否耐药
    下载: 导出CSV

    表  4  568株结核分枝杆菌对二线抗结核药耐药情况

    Table  4.   Drug resistances of 568 M. tuberculosis strains to second-line anti-TB drugs

     耐药类型初治患者分离株(n=463)复治患者分离株(n=105)合计(n=568)χ2P
    菌株数(株)耐药率(%)菌株数(株)耐药率(%)菌株数(株)耐药率(%)
    任意耐药316.7087.62396.87 0.114 0.735
     OFL224.7576.67295.11 0.648 0.421
     MXF275.8387.62356.16 0.473 0.492
     KAN 71.5100.00 71.23 0.359a
     AMI 61.3000.00 61.06 0.599a
    单药耐药 61.3010.95 71.23<0.001>0.999
     OFL 00.0000.00 00.00
     MXF 51.0810.95 61.06 >0.999a
     KAN 10.2200.00 10.18 >0.999a
     AMI 00.0000.00 00.00
    多药耐药255.4076.67325.63 0.258 0.611
     OFL+MXF194.1076.67264.58 0.767 0.381
     KAN+AMI 30.6500.00 30.53 >0.999a
     OFL+MXF+KAN+AMI 30.6500.00 30.53 >0.999a
     Pre-XDR-TB 71.5143.81111.94 1.323 0.250
     XDR-TB 20.4300.00 20.35 >0.999a
      注:OFL.氧氟沙星;MXF.莫西沙星;KAN.卡那霉素;AMI.阿米卡星;a.由Fisher确切概率法算得P值;−.无法计算;任意耐药指经体外药敏试验证实结核分枝杆菌对指定的抗结核药物耐药,而不考虑对其他药物是否耐药;Pre-XDR-TB.广泛耐药结核前期;XDR-TB.广泛耐药结核
    下载: 导出CSV

    表  5  2013-2017年湖南省耒阳市结核分枝杆菌的耐药趋势比较

    Table  5.   Drug resistance trend of M. tuberculosis in Leiyang from 2013 to 2017

    耐药模式2013年(n=165)2014年(n=94)2015年(n=140)2016年(n=86)2017年(n=83)趋势χ2P
    INH19(11.52)12(12.77)23(16.43)15(17.44)7(8.43) 0.0310.860
    RIF10(6.06) 12(12.77)11(7.86) 7(8.14)8(9.64) 0.3530.552
    EMB4(2.42)5(5.32)2(1.43)4(4.65)4(4.82) 0.6230.430
    SM12(7.27) 10(10.64)11(7.86) 12(13.95)7(8.43) 0.6430.423
    OFL2(1.21)3(3.19)8(5.71) 9(10.47)7(8.43)11.2990.001
    MXF5(3.03)3(3.19)9(6.43)10(11.63)8(9.64) 8.5850.003
    AMI1(0.61)1(1.06)2(1.43)2(2.33)0(0.00) 0.0570.811
    KAN1(0.61)1(1.06)3(2.14)2(2.33)0(0.00) 0.0920.762
    MDR-TB7(4.24)8(8.51)9(6.43)5(5.81)7(8.43) 0.9370.333
    Pre-XDR-TB2(1.21)1(1.06)2(1.43)2(2.33)4(4.82) 3.2580.071
    XDR-TB0(0.00)1(1.06)0(0.00)1(1.16)0(0.00) 0.0930.760
    DR-TB27(16.34)16(17.02)37(26.43)25(29.07)15(18.07) 2.4360.119
      注:括号外数据是菌株数,括号内数据是耐药率;INH. 异烟肼;RIF. 利福平;EMB. 乙胺丁醇;SM. 链霉素;OFL. 氧氟沙星;MXF. 莫西沙星;AMI. 阿米卡星;KAN. 卡那霉素;MDR-TB. 耐多药结核;Pre-XDR-TB. 广泛耐药结核前期;XDR-TB. 广泛耐药结核;DR-TB. 耐药结核
    下载: 导出CSV
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