Isolation of genetically distinct strains within the same species during treatment of MAC 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 pre-treatment isolates throughout the course of MAC-PD treatment. RESEARCH QUESTION What is the frequency of genetically distinct strains identified within the same species among pre- and on-treatment isolates in patients with MAC-PD? STUDY DESIGN AND METHODS We serially collected pre- and on-treatment clinical isolates from patients with MAC-PD treated for over one month from November 2019 to October 2022 at a tertiary hospital in South Korea. We utilized multilocus sequence typing (MLST) genotypic analysis to determine whether the on-treatment isolate was a genetically different strain compared with the pre-treatment isolate. RESULTS Among 327 enrolled patients, we identified the on-treatment isolates of 198 patients as the same species as the pre-treatment 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 revealed the presence of a genetically different strain among the on-treatment isolates at least once in 24.7% (49/198) of patients (95% confidence interval, 18.9-31.4) compared to the pre-treatment 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.