Summary

Mycobacterium xenopi is an increasingly recognized opportunistic lung pathogen that is difficult to treat. Infections often occur in patients with pre-existing health conditions and can present substantial diagnostic and therapeutic challenges. A deeper understanding of its genetic diversity and resistance mechanisms is essential for optimal patient management and for clarifying potential transmission routes. By analyzing 76 whole-genome sequences together with detailed clinical information and phenotypic drug-susceptibility data, this study substantially expands the available genomic repertoire for M. xenopi. While clinical relevance was limited in our cohort, most guideline-recommended antimicrobial agents showed good efficacy in vitro. The detection of closely related strains might point toward a common environmental source of infection. These findings highlight the need for continued surveillance and provide a comprehensive foundation that supports more accurate monitoring, improved understanding of disease behavior, and future investigations into M. xenopi pathogenicity.