Objective  To understand the combined mutation characteristics of isoniazid and rifampicin resistance genes of Mycobacterium tuberculosis in Guangxi and provide a basis for the molecular diagnosis and treatment of multidrug-resistant tuberculosis (MDR-TB).

  Methods  A total of 49 MDR strains and 459 fully sensitive strains of M. tuberculosis collected from 30 designated TB treatment institutions in Guangxi during 2017–2018 were selected for whole genome sequencing.

  Results  The consistent rate between the MDR phenotype and the combined mutation of genes was 71.43%. The single gene mutation rate and combined gene mutation rate were higher in the MDR strains than in the fully sensitive strains (χ²=5.753, P=0.016; χ²=284.034, P<0.001). The single gene mutation rates of katG and rpoB were higher in the MDR strains than in the fully sensitive strains (χ²=7.524, P=0.006; χ²=4.353, P=0.037). Combined mutations in katG＋rpoB genes were higher in the MDR strains than in the fully sensitive strains (χ²=279.956, P<0.001). Among the distribution of combined gene mutations, mutations at the katG315＋rpoB450 and katG315＋rpoB445 loci accounted for 40.82% (20/49), and the combined mutation rate of gene loci in both forms was higher in the MDR strains than in the fully sensitive strains (χ²=144.232, P<0.001; χ²=19.014, P<0.001).

  Conclusion  Detection of combined mutations of resistance genes to isoniazid and rifampicin can be used as an important method for MDR screening in Guangxi. Isoniazid and rifampicin resistance gene mutations of M. tuberculosis in Guangxi were mainly caused by mutations at the loci of katG315, rpoB450 and rpoB445, while the gene combined mutations were mainly in the form of katG＋rpoB. Mutations at the katG315＋rpoB450 and katG315＋rpoB445 loci are the main molecular mechanisms of MDR in Guangxi.