Genotyping of 1,189 multidrug-resistant Mycobacterium tuberculosis isolates collected across Argentina from 2013–2022 reveals that four dominant strains — M, Ra, Rb, and Callao2 — account for 45.9% of newly diagnosed MDR-TB cases. The historically dominant M strain is declining, while the Callao2 strain, likely imported from Peru, has expanded sharply in recent years. The Rb strain shows both wide geographic spread and a striking association with transgender women. Most cases belonged to identifiable transmission clusters, with orphan (unclustered) cases linked to poor treatment adherence and foreign-born patients. Pre-XDR and XDR proportions remain relatively low, a cautiously encouraging signal.

This decade-long molecular surveillance effort represents one of Latin America's most comprehensive MDR-TB genomic datasets, providing a critical baseline as Argentina transitions toward full whole-genome sequencing (WGS)-based monitoring. The Callao2 finding underscores how cross-border movement reshapes regional TB epidemiology — a dynamic increasingly relevant as climate and migration patterns shift. The strong Rb-transgender women association highlights how structural vulnerability concentrates infectious disease burden in marginalized populations, demanding targeted public health responses beyond antimicrobial stewardship alone. Limitations include the mixed methodology (PCR-based alongside WGS), which may introduce genotyping inconsistencies, and the observational, retrospective design precludes causal inference about transmission drivers. As a preprint posted on medRxiv and not yet peer-reviewed, these findings — particularly the genomic transmission chain analyses described as "preliminary" — should be interpreted cautiously until independent validation. Still, this work is meaningfully confirmatory and operationally valuable for regional TB control strategy.