[Drug resistance of clinical Mycobacterium tuberculosis isolates and molecular characteristics of rifampicin-resistant isolates from elderly pulmonary tuberculosis patients in Beijing, 2024].

Objective: To analyze the drug resistance spectrum of clinical isolates of Mycobacterium (M.) tuberculosis and the mutations in drug resistance-related genes in the genomic sequences of rifampicin-resistant isolates from elderly pulmonary tuberculosis (TB) patients in Beijing in 2024. Methods: A total of 474 M. tuberculosis isolates from elderly pulmonary TB patients were included. Drug susceptibility testing against 10 anti-TB drugs was performed with microbroth dilution method. Whole-genome sequencing (WGS) was performed for 27 rifampicin-resistant isolates to systematically characterize resistance-associated gene mutations and genotype-phenotype consistency. Results: The total drug resistance rate was 24.26% in the 474 M. tuberculosis isolates. The resistance rate was significantly higher in retreatment patients (44.00%) than in new patients (23.16%), and a higher multidrug resistance rate was observed in men (6.75% vs. 2.03%). WGS revealed that all the rifampicin-resistant strains belonged to lineage 2 (East Asian lineage), with rpoB p.Ser450Leu (55.56%) being the most prevalent mutation. Consistency between WGS and phenotypic drug susceptibility was 96.30% for isoniazid, pyrazinamide, and rifampicin, but was low for ethambutol (22.22%). Conclusions: The drug resistance of M. tuberculosis was severe in elderly pulmonary TB patients in Beijing, which was associated with treatment history and gender. Rifampicin-resistant strains showed lineage 2 clustering, indicating a risk for local transmission. The resistance genotypes detected by WGS were highly consistent with the phenotypic drug susceptibility of isoniazid and pyrazinamide, but showed low consistency with ethambutol.