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oai:docta.ucm.es:20.500.14352/935132025-02-27T00:56:36Zcom_20.500.14352_14col_20.500.14352_15

Griffith, David Brown-Elliott, Barbara Langsjoen, Brett Zhang, Yansheng Pan, Xi Girard, William Nelson, Kenwyn Caccitolo, James Álvarez Sánchez, Julio Shepherd, Sara Wilson, Rebecca Graviss, Edward Wallace, Richard 2024-01-17T08:32:11Z 2024-01-17T08:32:11Z 2006 Griffith, D. E., Brown-Elliott, B. A., Langsjoen, B., Zhang, Y., Pan, X., Girard, W., Nelson, K., Caccitolo, J., Alvarez, J., Shepherd, S., Wilson, R., Graviss, E. A., & Wallace, R. J., Jr (2006). Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. American journal of respiratory and critical care medicine, 174(8), 928–934. https://doi.org/10.1164/rccm.200603-450OC 1073-449X 10.1164/rccm.200603-450oc https://hdl.handle.net/20.500.14352/93513 1535-4970 https://doi.org/10.1164/rccm.200603-450OC Rationale: The clinical features and outcome of macrolide-resistant Mycobacterium avium complex (MAC) lung disease are not known. Objectives: Characterize patients, treatment, and isolates in macrolide-resistant MAC lung disease. Methods: Retrospective chart review, susceptibility testing, molecular fingerprinting, and DNA sequence analyses of resistant MAC isolates. Measurements and main results: We identified 51 patients over a 15-yr period with clarithromycin-resistant MAC (minimum inhibitory concentration (MIC)>or=32 microg/ml) lung disease at a single referral center. Twenty-four (47%) patients had nodular disease with bronchiectasis and 27 (53%) had upper lobe cavitary disease. Most patients (77%) had M. intracellulare. Sequencing of the 23S r-RNA gene showed 49 of 51 isolates (96%) with the expected mutation in adenine 2058 or 2059. Risk factors for resistance included macrolide monotherapy or combination with a quinolone only (39/51 or 76%). Macrolide resistance developed in 12 of 303 (4.0%) patients started on the American Thoracic Society-recommended two companion drugs, with no risk difference in clarithromycin versus azithromycin and daily versus intermittent therapy. Sputum conversion with macrolide-resistant MAC occurred in 11 of 14 (79%) patients who received more than 6 mo of injectable aminoglycoside therapy and lung resection, compared with 2 of 37 (5%) who did not. The 1-yr mortality in patients who remained culture positive was 34% (13/38) compared with 0% (0/13) of patients who became culture negative (converted). Conclusions: Macrolide resistance rarely occurs in patients also receiving ethambutol and a rifamycin. Macrolide-resistant MAC lung disease requires aggressive drug and surgical therapy for cure. eng http://creativecommons.org/licenses/by-nc-nd/4.0/ restricted access Attribution-NonCommercial-NoDerivatives 4.0 International Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease journal article