treatment, and few were clearly associated with community transmission. These findings suggest an additional diagnostic tool, such as the Xpert MTB/XDR cartridge or line-probe assay (LPA), in addition to Xpert MTB/RIF, and new oral regimens, including bedaquiline and pretomanind, are needed for effective surveillance and treatment/management of MDR TB in Mynamar. Further studies are also required to investigate apparent cases of independent emergence and community transmission of MDR TB in Yangon. Consistent with previous reports on lineage 2 from neighboring countries, this study identified a strong association between lineage 2 M. tuberculosis and drug resistance (14–17). There was strong agreement between WGS (presence of resistance-conferring mutations) and phenotypic DST to isoniazid and rifampin in this study (18). These findings indicate quality assurance in the TB laboratory diagnostic service provided by the Myanmar National Tuberculosis Reference Laboratory. The Xpert MTB/RIF assay has been effective in the simultaneous detection of TB and resistance to rifampin. Because it can provide a diagnosis for a patient within 2 hours, GeneXpert is critical in TB control in high-burden settings. One of the limitations of current cartridges for Xpert is that resistance to isoniazid is assumed when rifampin resistance is detected. This approach captures a large portion of drug-resistant TB cases during diagnosis. However, for a few case-patients, which includes patients who have isoniazid resistance without concurrent rifampin resistance (14% in this study and 9.4% in the recently reported multicountry study [19]), treatment with a first-line regimen can contribute to the emergence of further drug resistance. We previously reported that a patient with undiagnosed isoniazid resistance without concurrent rifampin resistance received a first-line treatment regimen that resulted in development of MDR TB (20). This finding highlights the limitations and real-world consequences of basing treatment decisions solely on results of the GeneXpert MTB/RIF system in a high-burden setting, where hundreds of cases are reported daily. This limitation is a serious impediment to controlling the spread of more extensive drug resistance (21). For example, although Xpert MTB/RIF can correctly diagnose RR MDR cases, it cannot detect pre-XDR and XDR cases. As identified in this study, 20% of rifampin-resistant cases identified by GeneXpert were pre-XDR (17%) and XDR (3%) cases, suggesting that ≈1 of 5 patients received limited treatment on the basis of treatment guidelines at the time of the study. Most case-patients (including pre-XDR and XDR patients) in this study had drug-resistant isolates that were not closely related (genomically unlinked), which is suggestive of independent emergence of drug resistance because of limited diagnosis or treatment, as well as patient noncompliance. This finding is in contrast to previous studies from other high burden settings, such as China and South Africa, which showed a high proportion of drug-resistant cases that were genomically linked, suggesting community transmission. Although it is possible that we simply did not have a high enough sampling fraction of all drug-resistant cases in the population under study, a high number of unclustered drug-resistant cases could be caused by differences in population density; the North, East, and West sections of Yangoon are in an urban industrial setting. These districts have a considerable