目的 考察靶向下一代测序分析耐药结核病使用抗结核药物后的耐药基因突变特征。方法 收集2022年2月—2023年8月南宁市第四人民医院结核科收治的87例结核病患者的菌株。以表型药物敏感性试验结果为参照标准，采用靶向下一代测序检出利福平、异烟肼、链霉素和乙胺丁醇的耐药突变基因分布、诊断效能，与Xpert MTB/RIF比较对利福平耐药的诊断效能。结果 利福平耐药基因突变类型以Ser531Leu（rpoB）为主，异烟肼耐药基因突变类型以Ser315Thr（katG）为主，链霉素耐药基因突变类型以Lys43Arg（rpsL）为主，乙胺丁醇耐药基因突变类型以Met306Val（embB）为主。以表型药物敏感性试验结果为参照标准，靶向下一代测序对利福平、异烟肼、链霉素和乙胺丁醇的准确率均大于80%，Xpert MTB/RIF检测利福平耐药的各指标均低于靶向下一代测序。结论 靶向下一代测序诊断利福平、异烟肼、链霉素和乙胺丁醇耐药性表现出较高的敏感度、特异度和准确率。

Objective To explore the mutation characteristics of drug-resistant genes in drug-resistant tuberculosis patients treated with antituberculosis drugs by targeting next generation sequencing analysis. Methods The strains from 87 tuberculosis patients admitted to the Tuberculosis Department of Nanning Fourth People's Hospital from February 2022 to August 2023 were collected. Based on the results of phenotype drug sensitivity tests, targeting next generation sequencing analysis was used to detect the distribution and diagnostic efficacy of resistance mutation genes for rifampicin, isoniazid, streptomycin, and ethambutol. The diagnostic efficacy for rifampicin resistance was compared with Xpert MTB/RIF. Results The mutation types of rifampicin resistance genes were mainly Ser531Leu (rpoB), isoniazid resistance genes were mainly Ser315Thr (katG), streptomycin resistance genes were mainly Lys43Arg (rpsL), and ethambutol resistance genes were mainly Met306Val (embB). Based on the results of phenotype drug sensitivity tests, the accuracy of targeting next generation sequencing analysis results for rifampicin, isoniazid, streptomycin, and ethambutol were greater than 80%. The Xpert MTB/RIF detection of rifampicin resistance indicators was lower than that of targeting next generation sequencing analysis. Conclusion Targeting next generation sequencing analysis has shown high sensitivity, specificity, and accuracy in diagnosing resistance to rifampicin, isoniazid, streptomycin, and ethambutol.

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广西自然科学基金资助项目（2023GXNSFAA026022）；广西生健康委员会自筹经费科研课题（Z-A20231211）