Molecular Epidemiology of Drug-Resistant Tuberculosis in Shantou, China: Associations between Drug Resistance and Genotypic Variation

Background Drug-resistant tuberculosis (DR-TB) is a major global health threat, particularly in resource-limited regions. Understanding lineage-specific mutations is critical for improving diagnostics and guiding precision treatment. Methods Drug susceptibility testing was performed using Löwenstein-Jensen medium. Resistance-associated gene fragments were amplified via PCR, and mutation sites were analyzed using SnapGene. Genotyping was conducted using IS6110 and 8-locus MIRU-VNTR, followed by phylogenetic analysis (MEGA11, Neighbor-Joining method). Fisher’s exact test assessed genotype-mutation and phenotype-resistance correlations. Results We analyzed 148 MTB isolates from Shantou, China (2024). Resistance prevalence was 31.8% (47/148), with 98.6% (146/148) harboring mutations. Highest resistance was to isoniazid (20.9%), followed by streptomycin (10.1%), rifampicin (6.2%), and ethambutol (6.2%). Retreated cases (20.4%) showed significantly higher resistance than new cases ( p  < 0.05). Key mutations included katG Arg463Leu (66.2%) and gyrA Ser95Thr (98.0%). Lineage 2 strains were the dominant transmitted strains in Shantou, carrying only inhA , rpsL , rrs , and pncA resistance-associated mutations. MIRU-VNTR identified 134 genotypes (clustering rate: 9.46%), of which 8 clusters shared the same resistance mutation profile. Conclusions Retreatment cases pose a higher DR-TB risk in this region, with notable isoniazid resistance. Resistance mutation patterns are regional and consistent with Erdman and CDC1551 standard strains. Integration of genotyping and resistance data may improve the efficiency of precision therapy and transmission monitoring. Enhanced molecular surveillance, standardised treatment and optimised retreatment regimens are recommended to control the spread of DR-TB.