The emergence of drug-resistant TB remains a global health threat, with only one-third of individuals estimated to have multi-drug (MDR) or rifampicin-resistant (RR) TB diagnosed and treated annually. While culture-based methods remain the standard for drug susceptibility testing (DST), they are not widely available and have long turnaround times for results, resulting in delays in diagnosis, treatment failure, and ongoing transmission of resistant strains. In 2023, the WHO recommended using targeted next-generation sequencing (tNGS) for detecting and managing drug-resistant TB. ASLM organized a four-part series to help countries share best practices for implementing tNGS. In the fourth session of the series, Dr. Sofia Viegas presented a case study illustrating the critical role of genomic surveillance in uncovering hidden drug-resistant patterns. A five-year analysis of isolates from patients with rifampicin resistance TB showed that bedaquiline resistance increased fourfold during the review period, from 3% to 14%, and was also found in isolates without fluroquinolone resistance. A third of the bedaquiline resistant strains had the rpoB Ile491Phe/I491F mutation, that is not picked up by current molecular tools. Additionally, the analysis revealed that bedaquline resistant strains had been circulating prior to the introduction of bedaquiline in the country, suggesting cross-border spread from countries that had introduced the drug earlier. This analysis highlighted the urgent need to strengthen capacity for sequencing-based surveillance to enable rapid detection of DR-TB and guide treatment decisions. Please follow the links here to view the recorded ECHO session and download the presentation slides.