Prevalence and Genetic Profiling of Second-line Drug Resistant Tuberculosis at the Tertiary Care Center of Northern India.

Abstract

The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicates control efforts. We investigated the prevalence and genetic patterns of pre-XDR and XDRTB, by employing second-line line probe assays (SL-LPA). This prospective cohort study was conducted at the Intermediate Reference Laboratory, from November 2023 to May 2024. We screened 1253 samples via Genxpert followed by florescence microscopy, and mutational/resistance analysis via the GenoType MTBDRplus/FL-LPA (first line-line probe assay) and MTBDRsl/SL-LPA for the mutation patterns. We identified 355 rifampicin drug-resistant TB isolates, 260 of which were smear positive samples obtained for FL-LPA and SL-LPA. Finally, 255 MDR/RR-TB patients were analyzed and 73(28.62%) patients exhibited second-line drug (SLD) resistance. Among the cases, 65(89.04%) were found to be resistant solely to fluoroquinolones (FQ), whereas 3(4.11%) were resistant only to aminoglycosides (pre-XDR TB). However, 5(6.8%) patients were resistant to both FQ and aminoglycosides (XDR-TB). We also found that males 44(60.37%) were more affected by SLD resistance than 29(39.72%) females, however SLD resistant females were younger than males (26.97 ± 14.84 vs. 35.84 ± 15.26, p = 0.016). The number of previously treated patients were significantly greater in SLD-resistance than in SLD-sensitive patients. The most common mutation in the gyrA gene was D94G, which was observed in 52(71.23%) cases, followed by A90V in 10(13.69%), D94N and D94A in 4(5.48%), whereas the rrs gene presented the rrsMUT1 (A1401G) mutation in 7(9.58%) and the rrsMUT2(G1484T) mutation in 1(1.37%) of SLD-resistant patients. The alarming rate of SLD-resistance among MDR-TB patients highlights the need for improved management strategies focused on early and accurate diagnosis of DR-TB.