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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (05) : 434 -439. doi: 10.3877/cma.j.issn.1674-1358.2018.05.004

所属专题： 文献；

论著

人类免疫缺陷病毒/结核分枝杆菌双重感染者结核分枝杆菌分离株一线药物耐药特征
郭倩1, 朱召芹1, 钱雪琴1, 金鑫1, 苏俊1, 张腾飞1, 魏剑浩1,†()   
  1. 1. 201508　上海，上海市公共卫生临床中心医学检验科
  • 收稿日期:2018-01-22 出版日期:2018-10-15
  • 通信作者: 魏剑浩
  • 基金资助:
    上海市卫生计划和生育委员会科研项目(No. 20164Y0226); 上海市公共卫生临床中心科研课题(No. KY-GW-2017-10); 传染病预防控制国家重点实验室开放课题(No. 2016SKLID303)

First-line drug resistance characteristics of Mycobacterium tuberculosis isolates from patients with human immunodeficiency virus/Mycobacterium tuberculosis coinfection

Qian Guo1, Zhaoqin Zhu1, Xueqin Qian1, Xin Jin1, Jun Su1, Tengfei Zhang1, Jianhao Wei1,†()   

  1. 1. Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Shanghai 201508, China
  • Received:2018-01-22 Published:2018-10-15
  • Corresponding author: Jianhao Wei
  • About author:
    Corresponding author: Wei Jianhao, Email:
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郭倩, 朱召芹, 钱雪琴, 金鑫, 苏俊, 张腾飞, 魏剑浩. 人类免疫缺陷病毒/结核分枝杆菌双重感染者结核分枝杆菌分离株一线药物耐药特征[J/OL]. 中华实验和临床感染病杂志(电子版), 2018, 12(05): 434-439.

Qian Guo, Zhaoqin Zhu, Xueqin Qian, Xin Jin, Jun Su, Tengfei Zhang, Jianhao Wei. First-line drug resistance characteristics of Mycobacterium tuberculosis isolates from patients with human immunodeficiency virus/Mycobacterium tuberculosis coinfection[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(05): 434-439.

目的

分析人类免疫缺陷病毒(HIV)感染者的结核分枝杆菌(MTB)分离株对一线抗结核分枝杆菌药物的耐药特征，为临床治疗HIV/MTB双重感染提供参考依据。

方法

选取上海市公共卫生临床中心2012年1月至2016年12月收治的HIV合并MTB感染者154例(实验组)和单纯结核分枝杆菌感染者357例(对照组)，进行异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)、链霉素(STR)4种一线药物耐药性检测，比较两组患者MTB的总耐药率和总耐多药率，初始及获得性耐药、耐多药率。

结果

HIV/MTB双重感染组患者总耐药率(44.2%，68/154)、初始耐药率(42.2%，19/45)、初始耐多药率(13.3%，6/45)、STR总耐药率(31.8%，49/154)和初始耐药率(28.9%，13/45)显著高于单纯结核分枝杆菌感染组(33.9%、25.0%、3.8%、22.7%、11.4%)(P均<0.05)。INH、RFP、EMB耐药率与单纯结核分枝杆菌感染组差异无统计学意义(P均> 0.05)。单纯结核分枝杆菌感染组患者获得性耐药率(39.1%，88/225)和获得性耐多药率(19.1%，43/225)分别高于初始耐药率(25.0%，33/132)和初始耐多药率(3.8%，5/132)(χ2= 16.785、P < 0.001；χ2= 7.393、P = 0.004)。

结论

HIV/MTB感染者分离的MTB对一线抗结核分枝杆菌药物耐药率和耐多药率高，其中STR耐药最为严重，提示临床治疗应重视HIV/MTB双重感染者的结核耐药问题，及时采取预防措施和制定个体化治疗方案。

关键词: 人类免疫缺陷病毒, 结核分枝杆菌, 双重感染, 耐药特征
Objective

To investigate the drug resistance characteristics ofMycobacterium tuberculosis (MTB) isolates to four first-line antituberculous drugs from patients with human immunodeficiency virus (HIV)/MTB coinfection, and to guide the clinical treatment.

Methods

MTB strains were isolated from 154 cases with HIV/MTB coinfection (experimental group) and 357 cases with HIV-negative tuberculosis (control group) who were admitted to Shanghai Public Health Clinical Center between January 2012 and December 2016. The drug resistance patterns to isoniazide (INH), rifampicin (RFP), ethambutol (EMB) and streptomycin (STR) were analyzed. The total drug resistance, multi-drug resistance, initial resistance and acquired drug resistance were compared, respectively.

Results

Among the 154 MTB isolates from tuberculosis patients with HIV infection, the rate of total resistance (44.2%, 68/154), initial resistance (42.2%, 19/45) initial multidrug-resistance (13.3%, 6/45), STR total resistance (31.8%, 49/154) and STR initial drug resistance (28.9%, 13/45) were significantly higher than those of TB patients without HIV infection (33.9%, 25.0%, 3.8%, 22.7%, 11.4%, respectively; allP < 0.05). While the resistance to INH, RFP, EMB showed no statistically significant difference between the two groups (allP> 0.05). Among patients with TB without HIV infection, the rate of acquired drug resistance (39.1%, 88/225) and acquired multidrug-resistance (19.1%, 43/225) were significantly higher than initial resistance (25.0%, 33/132) and initial multidrug-resistance (3.8%, 5/132) (χ2= 16.785,P< 0.001;χ2= 7.393,P= 0.004).

Conclusions

The situation of drug resistance and multidrug resistance in HIV/MTB coinfected patients was serious, especially STR, which indicated that clinicians should pay attention to MTB drug resistance in HIV infected patients and take timely preventive measures as well as individual treatment.

Key words: Human immunodeficiency virus, Mycobacterium tuberculosis, Coinfection, Drug resistance characterization
表1 HIV/MTB双重感染组与单纯结核病组患者的一般资料[例(%)]
基本资料 HIV/MTB双重感染组(154例) 单纯结核病组(357例) 统计值 P值
性别[例(%)] ? ? χ2 = 1.655 0.121
? 男 130(84.4) 284(79.6) ? ?
? 女 24(15.6) 73(20.4) ? ?
年龄(±s，岁) 39.50 ± 12.90 42.22 ± 22.45 t = 1.710 0.088
治疗史[例(%)] ? ? χ2 = 2.857 0.055
? 初治 45(29.2) 132(37.0) ? ?
? 复治 109(70.8) 225(63.0) ? ?
标本类型[例(%)] ? ? ? ?
? 痰液 93(60.4) 219(61.3) χ2 = 0.041 0.457
? 血液 12(7.8) 6(1.7) χ2 = 11.825 0.001
? 脑脊液 11(7.1) 5(1.4) χ2 = 11.697 0.001
? 胸腹水 7(4.5) 21(5.9) χ2 = 0.371 0.354
? 穿刺液 7(4.5) 29(8.1) χ2 = 2.103 0.101
? 分泌物 6(3.9) 32(9.0) χ2 = 4.014 0.030
? 其他 18(11.7) 45(12.6) χ2 = 0.084 0.449
DST结果[例(%)] ? ? χ2 = 4.862 0.018
? 全敏感 86(55.8) 236(66.1) ? ?
? 耐药 68(44.2) 121(33.9) ? ?
MDR-TB [例(%)] 29(18.8) 48(13.4) χ2 = 2.439 0.078
表2 HIV/MTB双重感染组与单纯结核分枝杆菌感染组患者耐药情况[例(%)]
耐药 HIV/MTB双重感染组(154例) 单纯结核分枝杆菌感染病组(357例) χ2值 P值
全敏感 86(55.8) 236(66.1) 4.862 0.018
耐药 68(44.2) 121(33.9) ? ?
? MDR-TB 29/154(18.8) 48/357(13.4) 2.439 0.078
? 初始耐药 19/45(42.2) 33/132(25.0) 4.798 0.024
? 初始MDR-TB 6/45(13.3) 5/132(3.8) 5.246 0.032
? 获得性耐药 49/109(45.0) 88/225(39.1) 1.036 0.184
? 获得性MDR-TB 23/109(21.1) 43/225(19.1) 0.183 0.386
表3 HIV/MTB双重感染组与单纯结核分枝杆菌感染组患者多种药物耐药率[例(%)]
耐药 HIV/MTB双重感染组 单纯结核分枝杆菌感染组
初治(45例) 复治(109例) 合计(154例) 初治(132例) 复治(225例) 合计(357例)
任何耐药 ? ? ? ? ? ?
? INH 9(20.0) 36(33.0) 45(29.2) 21(15.9) 72(32.0) 93(26.1)
? RFP 9(20.0) 29(26.6) 38(24.7) 11(8.3) 51(22.7) 62(17.4)
? EMB 4(8.9) 21(19.3) 25(16.2) 6(4.5) 33(14.7) 39(10.9)
? STR 13(28.9) 36(33.0) 49(31.8) 15(11.4) 66(29.3) 81(22.7)
单药耐药 ? ? ? ? ? ?
? INH 2(4.4) 4(3.7) 6(3.9) 11(8.3) 6(2.7) 17(4.8)
? RFP 3(6.7) 4(3.7) 7(4.5) 4(3.0) 6(2.7) 10(2.8)
? STR 7(15.6) 5(4.6) 12(7.8) 6(4.5) 8(3.6) 14(3.9)
2种药物耐药 ? ? ? ? ? ?
? INH + RFP 1(2.2) 3(2.8) 4(2.6) 0(0.0) 4(1.8) 4(1.1)
? RFP + STR 0(0.0) 2(1.8) 2(1.3) 2(1.5) 2(0.9) 4(1.1)
? INH + EMB 0(0.0) 1(0.9) 1(0.6) 1(0.8) 2(0.9) 3(0.8)
? INH + STR 1(2.2) 6(5.5) 7(4.5) 4(3.0) 18(8.0) 22(6.2)
? EMB + STR 0(0.0) 2(1.8) 2(1.3) 0(0.0) 0(0.0) 0(0.0)
3种药物耐药 ? ? ? ? ? ?
? INH + RFP + EMB 0(0.0) 1(0.9) 1(0.6) 2(1.5) 4(1.8) 6(1.7)
? INH + RFP + STR 1(2.2) 4(3.7) 5(3.2) 0(0.0) 11(4.9) 11(3.1)
? INH + EMB + STR 0(0.0) 2(1.8) 2(1.3) 0(0.0) 3(1.3) 3(0.8)
4种药物耐药 ? ? ? ? ? ?
? INH + RFP + EMB + STR 4(8.9) 15(13.8) 19(12.3) 3(2.3) 24(10.7) 27(7.6)
合计 19(42.2) 49(45.0) 68(44.2) 33(25.0) 88(39.1) 121(33.9)
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