Characterization of isoniazid resistance and genetic mutations in isoniazid-resistant and rifampicin-susceptible Mycobacterium tuberculosis in China  

作　　者：Dongxin Liu Bing Zhao Yang Zheng Xichao Ou Shengfen Wang Yang Zhou Yuanyuan Song Hui Xia Qiang Wei YanLin Zhao 

机构地区：[1]National Pathogen Resource Center,Chinese Center for Disease Control and Prevention,Beijing 102206,China [2]National Tuberculosis Reference Laboratory,National Center for Tuberculosis Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China

出　　处：《Infectious Medicine》2024年第3期23-29,共7页感染医学（英文）

基　　金：National Key Research and Development Project(2022YFC2305200,2022YFC2602200);Natural Science Foundation of Shenzhen(JCYJ20210324130009024)。

摘　　要：Background Patients with tuberculosis resistant to isoniazid but susceptible to rifampicin(Hr-Rs TB)remain a neglected demographic,despite a high disease burden and poor outcomes of these patients.The aim of this study was to investigate the characteristics of isoniazid-resistance-related mutations in Mycobacterium tuberculosis and resistance rates to drugs included in WHO-recommended regimens for Hr-Rs patients.Methods Mycobacterium tuberculosis isolates(n=4922)obtained from national tuberculosis drug-resistance surveillance were subjected to whole-genome sequencing to identify Hr-Rs strains.The minimal inhibitory concentrations(MICs)were established for the Hr-Rs strains to determine the isoniazid resistance levels.We also identified drug-resistance-associated mutations for five drugs(fluoroquinolones,ethambutol,pyrazinamide,streptomycin,and amikacin)in the Hr-Rs strains.Results Of the 4922 strains,384(7.8%)were Hr-Rs.The subculture of seven strains failed,so 377(98.2%)strains underwent phenotypic MIC testing.Among the 384 genotypic Hr-Rs strains,242(63.0%)contained the katG Ser315Thr substitution;115(29.9%)contained the-15C>T in the promoter region of the fabG1 gene;and 16(4.2%)contained Ser315Asn in the katG gene.Of the 239 strains with the Ser315Thr substitution,229(95.8%)had MIC≥2µg/mL,and of the 114 strains with the-15C>T mutation,103(90.4%)had 0.25µg/mL≤MIC≤1µg/mL.The genotypic resistance rates were 0.8%(3/384)for pyrazinamide,2.3%(9/384)for ethambutol and fluoroquinolones;39.6%(152/384)of the strains were resistant to streptomycin,but only 0.5%(2/384)of the strains were resistant to amikacin.Conclusion Ser315Thr in katG was the predominant mutation conferring the Hr-Rs phenotype,followed by the fabG1-15C>T mutation.The combination of rifampicin,pyrazinamide,ethambutol,and levofloxacin should be effective in the treatment of patients with Hr-Rs tuberculosis because the resistance rates for these drugs in China are low.

关 键 词：Mycobacterium tuberculosis Mono-isoniazid resistance Whole-genome sequencing Resistance mutation 

分 类 号：R51[医药卫生—内科学]