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- Title
Development of Macrolide Resistance and Reinfection in Refractory Mycobacterium avium Complex Lung Disease.
- Authors
Jhun, Byung Woo; Kim, Su-Young; Moon, Seong Mi; Jeon, Kyeongman; Kwon, O Jung; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung
- Abstract
<bold>Rationale: </bold>Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.<bold>Objectives: </bold>The 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.<bold>Methods: </bold>Among 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.<bold>Measurements and Main Results: </bold>The 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.<bold>Conclusions: </bold>Refractory 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).
- Publication
American Journal of Respiratory & Critical Care Medicine, 2018, Vol 198, Issue 10, p1322
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201802-0321OC