American journal of respiratory and critical care medicine · 2018
Development of Macrolide Resistance and Reinfection in Refractory Mycobacterium avium Complex Lung Disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
RATIONALE: Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.
OBJECTIVES: 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.
METHODS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: 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).
OBJECTIVES: 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.
METHODS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: 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).