Multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrier for the Stop TB plan. To identify risk factors for treatment outcome and cluster transmission of MDR/RR-TB, whole-genome sequencing (WGS) data of isolates from patients of the Chongqing Tuberculosis Control Institute were used for phylogenetic classifications, resistance predictions, and cluster analysis. A total of 223 MDR/RR-TB cases were recorded between 1 January 2018 and 31 December 2020. Elderly patients and those with lung cavitation are at increased risk of death due to MDR/RR-TB. A total of 187 MDR/RR strains were obtained from WGS data; 152 were classified as lineage 2 strains. Eighty (42.8%) strains differing by a distance of 12 or fewer single nucleotide polymorphisms were classified as 20 genomic clusters, indicating recent transmission. Patients infected with lineage 2 strains or those with occupations listed as "other" are significantly associated with a transmission cluster of MDR/RR-TB. Analysis of resistant mutations against first-line tuberculosis drugs found that 76 (95.0%) of all 80 strains had the same mutations within each cluster. A total of 55.0% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially against fluoroquinolones (63.6% [28 of 44]). Recent transmission of MDR/RR strains is driving the MDR/RR-TB epidemics, leading to the accumulation of more serious resistance along the transmission chains. IMPORTANCE The drug resistance molecular characteristics of MDR/RR-TB were elucidated by genome-wide analysis, and risk factors for death by MDR/RR-TB were identified in combination with patient information. Cluster characteristics of MDR/RR-TB in the region were analyzed by genome-wide analysis, and risk factors for cluster transmission (recent transmission) were analyzed. These analyses provide reference for the prevention and treatment of MDR/RR-TB in Chongqing.
Keywords: MDR/RR-TB; WGS; drug resistance; recent transmission.