Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease

David E. Griffith, Barbara A. Brown-Elliott, Brett Langsjoen, Yansheng Zhang, Xi Pan, William Girard, Kenwyn Nelson, James Caccitolo, Julio Alvarez, Sara Shepherd, Rebecca Wilson, Edward A. Graviss, Richard J. Wallace

Research output: Contribution to journalReview articlepeer-review

204 Scopus citations

Abstract

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) ≥ 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). 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.

Original languageEnglish (US)
Pages (from-to)928-934
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume174
Issue number8
DOIs
StatePublished - Oct 15 2006

Keywords

  • Aminoglycosides
  • Sequencing mutations
  • Surgery

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