Isolation of Genetically Distinct Strains Within the Same Species During Treatment of Mycobacterium Avium Complex Pulmonary Disease

BACKGROUND: Research on isolating genetically different strains within the same species in patients undergoing treatment for Mycobacterium avium complex (MAC) pulmonary disease (PD) is limited. We investigated the frequency of genetically distinct strains identified within the same species among on-treatment isolates compared with pretreatment isolates throughout the course of MAC-PD treatment. RESEARCH QUESTION: What is the frequency of genetically distinct strains identified within the same species among pretreatment and on-treatment isolates in patients with MAC-PD? STUDY DESIGN AND METHODS: We serially collected pretreatment and on-treatment clinical isolates from patients with MAC-PD treated for over 1 month from November 2019 to October 2022 at a tertiary hospital in South Korea. We used multilocus sequence typing (MLST) genotypic analysis to determine whether the on-treatment isolate was a genetically different strain compared with the pretreatment isolate. RESULTS: Among 327 enrolled patients, we identified the on-treatment isolates of 198 patients as the same species as the pretreatment isolates. The median treatment duration for the 198 patients was 14.4 months (interquartile range, 12.1-16.9 months). Of these patients, MLST analysis showed the presence of a genetically different strain among the on-treatment isolates at least once in 24.7% (49/198) of patients (95% CI, 18.9-31.4) compared with the pretreatment isolate. There were variations in the timing, frequency, and number of distinct strains in these 49 patients. INTERPRETATION: We identified a genetically distinct strain within the same species at least once in approximately 25% of patients in whom the same species was isolated after the initiation of anti-MAC-PD therapy. These findings may affect the determination of treatment outcomes and corresponding MAC-PD treatment strategies. CHEST 2025; 167(3):675-685