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Am J Respir Crit Care Med. 2006 Oct 15;174(8):928-34. Epub 2006 Jul 20.

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

Author information

1
The University of Texas Health Center, Department of Medicine, 11937 U.S. Hwy 271, Tyler, TX 75708, USA. david.griffith@uthct.edu

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)>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.

PMID:
16858014
DOI:
10.1164/rccm.200603-450OC
[Indexed for MEDLINE]

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