Cao Zhimin, Lan Yuanbo, Chen Ling, Xiang Min, Peng Zhiyuan, Zhang Jianyong, Zhang Hong
Tuberculosis Division, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, People's Republic of China.
Department of R & D, Z-BioMed, Inc, Rockville, MD, 20855, USA.
Infect Drug Resist. 2019 Sep 30;12:3093-3102. doi: 10.2147/IDR.S222943. eCollection 2019.
China is one of the high-burden countries for multidrug-resistant tuberculosis (MDR-TB), and pyrazinamide is one of the anti-TB drugs used for the shorter MDR-TB treatment regimen. The aim of this study was to determine the correlation between gene mutations and resistance to four first-line anti-TB drugs as well as treatment history in clinical isolates of .
clinical isolates were collected from 318 in-patients with smear-positive TB between October 2008 and September 2016 at a major hospital in Zunyi, Guizhou Province of China, and used for drug susceptibility testing against four first-line anti-TB drugs. Genomic DNA extracted from clinical isolates was used for PCR amplification and DNA sequencing of the gene.
Among 318 clinical isolates, 129 (40.6%), 170 (53.5%), 66 (20.8%) and 109 (34.3%) were resistant to rifampicin, isoniazid, ethambutol and streptomycin respectively. In addition, 124 clinical isolates were MDR-TB and 71.8% of them were previously treated cases. Sequencing results showed that 46.8% of MDR-TB and 2.2% of drug susceptible isolates harbored a mutation, and 52 types of mutations were detected from 64 isolates. The prevalence of mutations in isolates resistant to first-line anti-TB drugs and previously treated TB cases was significantly higher than that in drug-susceptible isolates and new cases of TB.
High prevalence of mutations in clinical isolates of from Zunyi, Guizhou Province of China, is correlated with resistance to four first-line anti-TB drugs, MDR-TB and previously treated TB cases.
中国是耐多药结核病(MDR-TB)高负担国家之一,吡嗪酰胺是用于较短程耐多药结核病治疗方案的抗结核药物之一。本研究旨在确定基因突变与四种一线抗结核药物耐药性以及临床分离株治疗史之间的相关性。
2008年10月至2016年9月期间,从中国贵州省遵义市一家大型医院的318例痰涂片阳性结核病住院患者中收集临床分离株,并用于对四种一线抗结核药物进行药敏试验。从临床分离株中提取的基因组DNA用于该基因的PCR扩增和DNA测序。
在318株临床分离株中,分别有129株(40.6%)、170株(53.5%)、66株(20.8%)和109株(34.3%)对利福平、异烟肼、乙胺丁醇和链霉素耐药。此外,124株临床分离株为耐多药结核病,其中71.8%为既往治疗病例。测序结果显示,46.8%的耐多药结核病分离株和2.2%的药物敏感分离株存在该基因突变,从64株分离株中检测到52种该基因突变类型。一线抗结核药物耐药分离株和既往治疗结核病病例中该基因突变的发生率显著高于药物敏感分离株和新发结核病病例。
中国贵州省遵义市临床分离株中该基因突变的高发生率与对四种一线抗结核药物耐药、耐多药结核病及既往治疗结核病病例相关。