Published ahead of print on July 20, 2006, doi:10.1164/rccm.200603-450OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200603-450OC
Clinical and Molecular Analysis of Macrolide Resistance in Mycobacterium avium Complex Lung DiseaseDepartments of Medicine, Microbiology, Thoracic Surgery, and Occupational Health Sciences, University of Texas Health Center, Tyler; and Department of Pathology, Baylor College of Medicine, Houston, Texas Correspondence and requests for reprints should be addressed to David E. Griffith, M.D., The University of Texas Health Center, Department of Medicine, 11937 U.S. Hwy 271, Tyler, TX 75708. E-mail: david.griffith{at}uthct.edu 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) 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.
Key Words: aminoglycosides • sequencing mutations • surgery This article has been cited by other articles:
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32 µg/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). 
