Abstract
陈蓉,李马超,赵丽丽,赵秀芹,刘海灿,刘志广,鲁瑶,邓云丽,陈紫昕,万康林,袁秀琴.167株耐多药结核分枝杆菌药物敏感谱分析[J].Chinese journal of Epidemiology,2020,41(5):764-769
167株耐多药结核分枝杆菌药物敏感谱分析
Analysis on drug sensitivity spectrum of 167 multidrug-resistant Mycobacterium tuberculosis in China
Received:November 21, 2019  
DOI:10.3760/cma.j.cn112338-20191121-00823
KeyWord: 耐多药结核病  药物敏感性试验  交叉耐药  基因型
English Key Word: Multidrug-resistant tuberculosis  Drug sensitivity test  Cross resistance  Genotype
FundProject:国家科技重大专项(2018ZX10302302001005)
Author NameAffiliationE-mail
Chen Rong School of Public Health, University of South China, Hengyang 421001, China
State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China 
 
Li Machao State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China  
Zhao Lili State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China  
Zhao Xiuqin State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China  
Liu Haican State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China  
Liu Zhiguang State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China  
Lu Yao School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China  
Deng Yunli School of Public Health, University of South China, Hengyang 421001, China
State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China 
 
Chen Zixin School of Public Health, University of South China, Hengyang 421001, China
State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China 
 
Wan Kanglin State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China wankanglin@icdc.cn 
Yuan Xiuqin School of Public Health, University of South China, Hengyang 421001, China wtjysh@126.com 
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Abstract:
      目的 了解耐多药结核分枝杆菌的药敏谱,为耐多药结核病(MDR-TB)的临床药物选择和防控提供科学依据。方法 选取既往收集的MDR-TB 167株,采用lysX基因测序方法进行基因分型,并采用微孔板药敏法及BACTECTM MGIT 960TM液体培养法对其进行13种抗结核药物的敏感性检测,分析不同基因型MDR-TB菌株与耐药表型的相关性及药物交叉耐药情况。采用χ2检验比较计数资料组间差异。结果 167株MDR-TB菌株对除异烟肼、利福平外11种抗结核药物总耐药率为95.81%,准广泛耐药结核病(pre-XDR)比例为31.14%(52/167),广泛耐药结核病比例为6.59%(11/167)。北京基因型中链霉素耐药率高于非北京基因型,差异有统计学意义(χ2=30.682,P<0.05),非北京基因型中pre-XDR比例高于北京基因型,差异有统计学意义(χ2=5.332,P<0.05);氧氟沙星耐药率和吡嗪酰胺耐药率在现代北京基因型与古典北京基因型中差异有统计学意义(χ2=4.105和χ2=3.912,P<0.05)。利福平与利福布汀存在交叉耐药,交叉耐药率为86.23%,且不同程度利福平耐药组间利福布汀耐药率差异有统计学意义(χ2=45.912,P<0.05)。氧氟沙星耐药与莫西沙星耐药有相关性、阿米卡星耐药与卡那霉素耐药有相关性,r分别为0.87和0.91。结论 MDR-TB菌株对11种抗结核药物呈高度耐药,且同类型药物之间交叉耐药较为严重;北京基因型菌株是MDR-TB的主要流行菌株,与链霉素耐药高度相关。
English Abstract:
      Objective To investigate the drugs-sensitivity spectrum of multidrug-resistant tuberculosis (MDR-TB) in China and provide a scientific evidence for the drug selection in clinical therapy and the control of MDR-TB. Methods A total of 167 strains of MDR-TB were included in this study. Every strain was genotyped by lysX gene sequencing and their sensitivity to 13 different anti-TB drugs was tested by using MicroDSTTM and BACTECTM MGIT 960TM liquid-culturing method. The association between drug resistance and genotypes as well as cross drug resistance was also analyzed. The results were analyzed by means of the comparison of enumeration data between two groups with χ2 test. Results The overall resistance rate of 167 MDR-TB strains to 11 anti-TB drugs, except isoniazide and rifampicin, was 95.81%, the rates of pre-extensive drug-resistance (pre-XDR) and extensive drug-resistance were 31.14%(52/167) and 6.59% (11/167), respectively. The streptomycin resistance rate of Beijing genotypes was significantly higher than that of the non-Beijing genotypes (χ2=30.682, P<0.05), while the pre-XDR proportion in Beijing genotypes was lower than that in non-Beijing genotypes (χ2=5.332, P<0.05). The resistance rates of Ofloxacin and Pyrazinamide in the modern Beijing genotype were significantly higher than those in classical ones (χ2=4.105 and χ2=3.912, P<0.05). In addition, the cross-resistance rate to rifampicin and rifabutin was 86.23%. A significant difference in drug-resistance rate to rifabutin was seen among groups with different levels of rifampicin resistance (χ2=45.912, P<0.05). There was positive correlation not only between ofloxac resistance and moxifloxac resistance, but also between amikacin resistance and kanamycin resistance, with the coefficient of 0.87 and 0.91, respectively. Conclusions In this study, we observed that there were high incidences of the resistance to 11 anti-TB drugs in 167 clinical MDR-TB strains and the cross resistance phenomena between drugs of the same type were quite serious. The majority of MDR-TB strains belonged to Beijing genotype, which was highly associated with streptomycin resistance.
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