• Am. J. Respir. Crit. Care Med. · Nov 2018

    Development of Macrolide Resistance and Reinfection in Refractory Mycobacterium avium Complex Lung Disease.

    • Byung Woo Jhun, Su-Young Kim, Seong Mi Moon, Kyeongman Jeon, Kwon O Jung OJ 0000-0003-4699-8665 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and., Hee Jae Huh, Chang-Seok Ki, Nam Yong Lee, Sung Jae Shin, Charles L Daley, and Won-Jung Koh.
    • 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and.
    • Am. J. Respir. Crit. Care Med. 2018 Nov 15; 198 (10): 1322-1330.

    RationalePatients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.ObjectivesThe aim of this study was to determine whether reinfection was a factor in the low incidence of macrolide resistance in patients with refractory MAC-LD.MethodsAmong 481 patients with treatment-naive MAC-LD who started antibiotic treatment between January 2002 and December 2013, we identified 72 patients with refractory disease, characterized by persistently positive sputum cultures despite ≥12 months of treatment. Molecular analyses of the 23S ribosomal RNA gene responsible for macrolide resistance and serial mycobacterial genotyping were performed using stored MAC isolates.Measurements And Main ResultsThe median duration of treatment was 32 months (interquartile range, 24-41 mo) in 72 patients. After treatment for a median of 33 months (interquartile range, 21-44 mo), macrolide resistance developed in 16 (22%) patients. Molecular analysis of isolates from 15 patients revealed that 80% (12 of 15) had a point mutation at position 2,058 or 2,059 of the 23S ribosomal RNA gene. Of the 49 patients who had stored pre- and post-treatment isolates, mycobacterial genotyping revealed that reinfection by new MAC strains occurred in 36 (73%) patients. New MAC strains were found in 24 (49%) patients, and mixed infections with original and new strains occurred in 12 (24%) patients. Only 13 (27%) patients had persistent infections with their original MAC strains.ConclusionsRefractory MAC-LD is commonly caused by reinfection with new strains rather than persistence of the original strain, which may explain the infrequent development of macrolide resistance in refractory MAC-LD. Clinical trial registered with www.clinicaltrials.gov (NCT00970801).

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