registration, had a TB-positive confirmation by GeneXpert, and provided written informed consent. Patients were excluded if their residential address was outside Yangon at the time of registration or they did not provide informed consent. We obtained a brief clinical report for each patient (basic demographics, residential address, history of TB treatment, HIV status, and random blood glucose testing results for diabetes mellitus). The Institutional Review Boards of the Department of Medical Research, Ministry of Health and Sports of Myanmar, and the Human Health Ethics Review Committee of the University of Otago (Dunedin, New Zealand) approved this study. Laboratory Procedures We collected all clinical sputum samples at the time of diagnosis and before commencement of treatment. We sent samples to the National Tuberculosis Reference Laboratory in Yangon for DST. Testing for resistance to isoniazid, rifampin, ethambutol, streptomycin, para-aminosalicylic acid, ethionamide, D-cycloserine, fluoroquinolones (ofloxacin, levofloxacin, capreomycin), and aminoglycosides (amikacin, kanamycin) was performed by using the proportion method on _TB_2001.288_eng.pdfExternal Link). We determined resistance to new and repurposed drugs (i.e., pyrazinamide, bedaquiline, pretomanid, delamanid, linezolid, and clofazimine) on the basis of genomic markers known to be associated with resistance (5,7,8). Clinicians were provided with the WGS and accompanying phenotypic DST data as soon as it was available, and clinical decisions were made entirely at their discretion. We extracted genomic DNA from cultures of single sputum specimens by using MoBio Microbial DNA Isolation Kits (https://www.qiagen.comExternal Link) and sequenced DNA by using Illumina MiSeq). All sequencing data from this study were deposited into the National Center for Biotechnology Information Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sraExternal Link; accession no. PRJNA638161).We performed genomic mapping by using Burrow-Wheeler Aligner-maximum exact matches (version 7.17-r1188; https://bio-bwa.sourceforge.netExternal Link) and the M. tuberculosis reference genome H37Rv (GenBank accession no. NC_000962.3). Mapping used a custom M. tuberculosis masking browser extensible data file to exclude highly repetitive GC-rich conserved domains. We used SAMtools and BCFtools utilities version 1.9 to call single-nucleotide polymorphisms (SNPs) (11). M. tuberculosis TB-Profiler version 2.8.2 (https://github.comExternal Link) was used to predict resistance to 17 drugs on the basis of genotyping of gene targets and classification to phylogenetic lineages by using SNP barcodes (7,8). Maximum-likelihood phylogenetic analyses were conducted by using RaxML, as implemented in the Gubbins pipeline version 2.3.4 (12). We used the online platform iTOL version 5.5 for annotation and management of phylogenetic trees (13). Isolates were considered closely related (genomically linked) if the pairwise distance between them was <12 SNPs (5). Statistical analyses were performed by using GraphPad Prism version 8.0 (https://www.graphpad.comExternal Link) and the χ2 test. A p value <0.05 was considered statistically significant. Results Over the recruitment period, 342 patients (194 with RR and 148 with RS M. tuberculosis) participated in the study; 33 case-patients were excluded because of