RT Journal Article
T1 Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease
A1 Griffith, David
A1 Brown-Elliott, Barbara
A1 Langsjoen, Brett
A1 Zhang, Yansheng
A1 Pan, Xi
A1 Girard, William
A1 Nelson, Kenwyn
A1 Caccitolo, James
A1 Álvarez Sánchez, Julio
A1 Shepherd, Sara
A1 Wilson, Rebecca
A1 Graviss, Edward
A1 Wallace, Richard
AB 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.
PB American Thoracic Society
SN 1073-449X
YR 2006
FD 2006
LK https://hdl.handle.net/20.500.14352/93513
UL https://hdl.handle.net/20.500.14352/93513
LA eng
NO 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
NO Supported by institutional funding at the University of Texas Health Science Center at Tyber (UTHCT).
NO University of Texas Health Science Center
DS Docta Complutense
RD 30 jul 2025