RpoB mutation patterns in Rifampicin-resistant tuberculosis: a Jiangxi Province study, 2021-2023

Antimicrobial resistance in Mycobacterium tuberculosis (M.tb) strains presents a significant challenge to global tuberculosis (TB) control efforts. This study was conducted to explore the distribution and prevalence of mutations at various sites within the 81 bp Rifampicin (RIF) resistance-determining region (RRDR) of the rpoB gene in M.tb, as detected by the Xpert MTB/RIF assay. This retrospective analysis encompassed 9,867 non-repeating patients diagnosed with TB between 2021 and 2023. Cases with RR detected by the Xpert were included in further detailed analysis. The study utilized Chi-square tests or Fisher's exact tests to identify statistically significant differences in demographic variables and the prevalence of rpoB gene mutations between RResistant TB (RR-TB) and non-RR-TB groups. Multiple logistic regression analysis was employed to examine the relationship between probe types and demographic variables, with a P-value of less than 0.05 considered statistically significant. Over the three-year study period, M. tb was identified in 2,927 cases, with 485 being RR-TB. While individuals aged ≥ 65 years constituted the largest absolute number of RR-TB cases, the highest relative risk was observed in children aged 5-14 years (OR = 2.68, 95% CI 1.16-6.22, P = 0.02) compared to the ≥ 65 reference group. probe E missing emerged as the predominant mutation site, particularly prevalent in pulmonary specimens and among individuals aged 55-64 years, with a statistically significant difference (P < 0.001). An upward trend in probe B mutations was also observed, reaching statistical significance (χ2 = 6.614, P = 0.037).This molecular epidemiological study has identified the mutation patterns within the rpoB gene that contribute to RR, as identified through the use of Xpert technology over a three-year span in Jiangxi Province. The insights gained are instrumental in informing individualized treatment regimens for RR-TB patients by correlating mutation locations with resistance levels (e.g., probe E mutations confer high-level resistance requiring second-line drugs, while probe B mutations like D435Y may confer low-level "disputed" resistance). This facilitates precision therapy, avoids unnecessary second-line treatments, and reduces transmission. Future advancements in technology, such as large-scale sequencing studies, could build upon these findings to further elucidate the genetic variations at play. Ultimately, these discoveries could be corroborated through rigorous in vitro and in vivo experimental research, reinforcing the foundation of our understanding and response to antimicrobial resistance in M.tb.