AUTHOR=Tan Jishan , Liu Lu , Wang Lu , Qu Yuanqing , Sun Zhiyong , Wang Qin , Liu Yuan TITLE=Case Report: First pulmonary infection caused by Mycobacterium colombiense in a non-immunosuppressed host with bronchiectasis: diagnosis facilitated by synergistic mNGS and culture JOURNAL=Frontiers in Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1671968 DOI=10.3389/fmed.2025.1671968 ISSN=2296-858X ABSTRACT=Mycobacterium colombiense, a rare slow-growing mycobacterium within the Mycobacterium avium complex (MAC), causes disseminated disease almost exclusively in immunocompromised hosts, with no prior reports of localized pulmonary infection in non-immunosuppressed individuals. A 47-year-old non-immunosuppressed male with bronchiectasis presented with progressive cough, night sweats, and fatigue. Computed tomography (CT) revealed bronchiectasis with nodules in the right middle and lower lobes. Empirical β-lactam therapy failed, and conventional bronchoalveolar lavage fluid (BALF) tests (smears, cultures, PCR) yielded no pathogens at 48 h. Although metagenomic next-generation sequencing (mNGS) of BALF detected a low number of M. colombiense sequences (eight reads), definitive confirmation was achieved through extended culture, which is considered the gold standard for the diagnosis of nontuberculous mycobacteria. This culture revealed acid-fast bacilli within 12 days (160 CFU), confirming the presence of viable M. colombiense. Subsequent mNGS of the isolated colonies further confirmed the species identity with high sequence reads (25,787 reads). Guideline-based triple therapy (guided by drug susceptibility testing and guidelines) with clarithromycin, rifampicin, and ethambutol achieved significant radiographic resolution at 24 weeks. This case demonstrates that M. colombiense pulmonary infection is diagnostically elusive and mimics non-specific respiratory syndromes. It defines the clinical features of this pathogen in non-immunosuppressed hosts and highlights the need for heightened surveillance for nontuberculous mycobacteria (NTM) in bronchiectasis patients, given the likelihood of underdiagnosis.