Page 67 - 《南京医科大学学报（自然科学版）》2026年第3期

第46卷第3期 南京医科大学学报（自然科学版）
2026年3月 Journal of Nanjing Medical University（Natural Sciences） ·375 ·

·临床研究·

利福平和利福布汀对 rpoB 基因突变而表型敏感的结核菌耐药

性研究

杨 燕 ，胡琴琴 ，刘 裔 ，黄 艳 ，张向荣 1
2
1*
1
1
南京中医药大学附属南京医院（南京市第二医院）结核科，检验检测中心，江苏 南京 210003
1 2
［摘 要］ 目的：研究利福平（rifampicin，RIF）和利福布汀（rifabutin，RFB）两种药物对rpoB基因突变而表型敏感的结核分枝杆
菌（Mycobacterium tuberculosis，MTB）耐药性的差异。方法：收集2022年1月—2024年12月南京中医药大学附属南京医院肺结
核患者痰液或肺泡灌洗液标本，经MTB培养、Xpert分子药敏检测及rpoB基因测序，筛选出RIF表型敏感、低度耐药及部分高度
耐药的rpoB 突变菌株，采用浓度梯度法测定RIF 和RFB 的最小抑菌浓度（minimum inhibitory concentration，MIC）。结果：共纳
入298 株分子和表型药敏均呈阳性菌株，分子药敏检测RIF 耐药的灵敏度为93.3%，特异度为94.6%，准确率为94.3%。在82
株分子耐药菌株中，96.3%检测出 rpoB 基因突变，常见的突变点为 531、526、511。琼脂固体药敏结果显示：S531L、H526Y、
H526R、H526Q、D516V对RIF高度耐药；S512G、S522L、L533P对RIF低度耐药；H526L、D516Y、L511P、P483L对RIF敏感。MIC
检测发现，仅H526L和L511P对两种药物均敏感；而S531L、L511P+H526Q双突变、H526D、D516Y、S512G、S522L、L533P、P483L
等突变对RIF耐药但对RFB敏感。整体上，rpoB突变株对数转换的RIF MIC（log2RIF⁃MIC）值［3.50（1.00，4.00）］显著高于对数
转换的 RFB MIC（log2 RFB⁃MIC）值［2.00（-3.00，3.75）］（Z=-4.481，P < 0.001）。结论：rpoB 突变位点差异导致 MTB 对 RIF 和
RFB耐药水平不同。相比RIF，RFB对多种rpoB突变株（如L511P、H526L、D516Y、S522L等）具有更低的MIC值及潜在的临床
有效性。通过对rpoB突变位点进行精准分析并评估其对RFB的敏感性，可为“分子耐药⁃表型敏感”的临床困境提供新思路，
并为利福霉素类药物的个体化分层治疗提供依据。
［关键词］ 分枝杆菌；表型药敏；基因突变；分层治疗；利福平；利福布汀
［中图分类号］ R52 ［文献标志码］ A ［文章编号］ 1007⁃4368（2026）03⁃375⁃09
doi：10.7655/NYDXBNSN251115

Study on the drug resistance to rifampicin and rifabutin in Mycobacterium tuberculosis
with rpoB gene mutation but phenotypically sensitive

1
1
2
1*
YANG Yan ，HU Qinqin ，LIU Yi ，HUANG Yan ，ZHANG Xiangrong 1
1 Department of Tuberculosis，Inspection and Testing Center，the Affiliated Nanjing Hospital of Nanjing University of
2
Chinese Medicine（Nanjing Second Hospital），Nanjing 210003，China
［Abstract］ Objective：To examine the variations in drug resistance between rifampicin（RIF）and rifabutin（RFB）in Mycobacterium
tuberculosis（MTB）with rpoB gene mutations but phenotypically sensitive. Methods：Sputum or bronchoalveolar lavage fluid samples
from pulmonary tuberculosis patients at the Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 2022
to December 2024 were collected. These samples underwent MTB culture，Xpert molecular drug susceptibility testing（DST），and rpoB
gene sequencing. Strains with rpoB mutations that were phenotypically sensitive，showed low⁃level resistance，or selected cases of high⁃
level resistance to RIF were screened. The minimum inhibitory concentrations（MIC）of RIF and RFB were determined using the
concentration gradient method. Results：A total of 298 strains were included，with both molecular and phenotypic DST being positive.
The molecular DST showed a sensitivity of 93.3% and a specificity of 94.6% for detecting RIF resistance，with an overall accuracy of
94.3%. Among 82 molecularly resistant strains，rpoB gene mutations were detected in 96.3%，with common mutation sites at codons
531，526，and 511. Agar⁃based phenotypic DST results showed that S531L，H526Y，H526R，H526Q，and D516V mutations conferred

［基金项目］ 南京市卫生科技发展专项资金项目（YKK23131）
通信作者（Corresponding author），E⁃mail：yangyan00103@126.com（ORCID：0000⁃0003⁃2491⁃0394）
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