河南省耐多药结核分枝杆菌的吡嗪酰胺耐药性及突变模式
Pyrazinamide Resistance and Mutation Patterns Among Multidrug-Resistant from Henan Province.
作者信息
Shi Jie, Su Ruyue, Zheng Danwei, Zhu Yankun, Ma Xiaoguang, Wang Shaohua, Li Hui, Sun Dingyong
机构信息
Henan Province Center for Disease Control and Prevention, Zhengzhou, Henan Province, People's Republic of China.
出版信息
Infect Drug Resist. 2020 Aug 20;13:2929-2941. doi: 10.2147/IDR.S260161. eCollection 2020.
PURPOSE
This study was designed to identify the phenotypic and genotypic characteristics of pyrazinamide (PZA) resistance among multidrug-resistant (MDR-TB) from Henan and to evaluate the efficacy of , and mutations in predicting PZA resistance.
MATERIALS AND METHODS
A total of 152 MDR strains were included in this study. The Bactec MGIT system was used to determine PZA susceptibility for all strains. The , and genes were sequenced to identify any mutations, and the sequences were then aligned with the sequence of standard strain H37Rv. Moreover, the correlations between PZA-resistant phenotypes and treatment outcomes were analysed.
RESULTS
Of the152 strains, 105 had a PZA-resistant phenotype, and 102 harboured the mutation. The PZA resistance rate was higher in the strains with resistance to all four first-line drugs and those that were pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR). A total of 100 different mutation patterns were identified, including 80 point mutations and 20 insertions/deletions, and 32 new mutation patterns were detected. In this study, 13 strains had multiple mutations. Of the11 PZA-resistant strains without mutations, two harboured the mutation, and one harboured the mutation. With PZA susceptibility results as the reference, single-gene sequencing had sensitivity of 89.52% and specificity of 89.36%. With the combination of and , the sensitivity increased to 92.38%, and the specificity remained the same. No significant differences were observed in the sputum smear/culture conversion rate between PZA-resistant patients and PZA-sensitive patients. However, PZA resistance was related to the time to sputum smear/culture conversion ( = 0.018).
CONCLUSION
The combination of , and was beneficial for the timely diagnosis of PZA resistance and could provide a laboratory basis for customizing treatment regimens for MDR-TB patients.
目的
本研究旨在鉴定河南耐多药结核病(MDR-TB)中吡嗪酰胺(PZA)耐药的表型和基因型特征,并评估katG、rpoB和embB基因突变在预测PZA耐药方面的效能。
材料与方法
本研究共纳入152株MDR菌株。使用Bactec MGIT系统测定所有菌株对PZA的敏感性。对katG、rpoB和embB基因进行测序以鉴定任何突变,然后将序列与标准菌株H37Rv的序列进行比对。此外,分析了PZA耐药表型与治疗结果之间的相关性。
结果
在152株菌株中,105株具有PZA耐药表型,102株存在katG突变。对所有四种一线药物耐药的菌株以及预广泛耐药(pre-XDR)和广泛耐药(XDR)的菌株中,PZA耐药率更高。共鉴定出100种不同的katG突变模式,包括80个点突变和20个插入/缺失,并检测到32种新的katG突变模式。在本研究中,13株菌株存在多个突变。在11株无katG突变的PZA耐药菌株中,2株存在rpoB突变,1株存在embB突变。以PZA敏感性结果为参考,单基因katG测序的敏感性为89.52%,特异性为89.36%。katG和rpoB联合检测时,敏感性提高到92.38%,特异性保持不变。PZA耐药患者和PZA敏感患者之间的痰涂片/培养转阴率未观察到显著差异。然而,PZA耐药与痰涂片/培养转阴时间相关(P = 0.018)。
结论
katG、rpoB和embB联合检测有利于PZA耐药的及时诊断,并可为MDR-TB患者制定个体化治疗方案提供实验室依据。
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