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

Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease 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 579.61 Aminoglycosides Sequencing mutations Surgery Microbiología médica 3201.03 Microbiología Clínica Supported by institutional funding at the University of Texas Health Science Center at Tyber (UTHCT). 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. University of Texas Health Science Center Depto. de Sanidad Animal Fac. de Veterinaria TRUE pub 2024-01-17T08:32:11Z 2024-01-17T08:32:11Z 2006 journal article VoR https://hdl.handle.net/20.500.14352/93513 1073-449X 10.1164/rccm.200603-450oc 1535-4970 eng 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 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ restricted access application/pdf American Thoracic Society