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

Am J Respir Crit Care Med. 2006 Oct 15;174(8):928-34. doi: 10.1164/rccm.200603-450OC. Epub 2006 Jul 20.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Infective Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Chaperonin 60
  • Chaperonins / genetics
  • Clarithromycin / therapeutic use
  • Drug Resistance, Bacterial*
  • Female
  • Humans
  • Macrolides / therapeutic use*
  • Male
  • Middle Aged
  • Mycobacterium avium Complex / drug effects*
  • Mycobacterium avium Complex / genetics
  • Mycobacterium avium Complex / isolation & purification
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Mycobacterium avium-intracellulare Infection / microbiology
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / microbiology
  • Polymerase Chain Reaction
  • Prognosis
  • RNA, Bacterial / genetics
  • Retrospective Studies


  • Anti-Infective Agents
  • Bacterial Proteins
  • Chaperonin 60
  • Macrolides
  • RNA, Bacterial
  • heat-shock protein 65, Mycobacterium
  • Chaperonins
  • Clarithromycin