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

Investigación publicada en American Journal of Respiratory and Critical Care Medicine

1 de octubre de 2006

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




Griffith DE., Brown-Elliott BA., Langsjoen B., Zhang Y., Pan X., Girard W., Nelson K., Caccitolo J., Alvarez J., Shepherd S., Willson R., Graviss EA. y Wallace RJ JR.




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

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


Participantes:

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Universidad ComplutenseServicio de Micobacterias (MYC). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

University of TexasUniversity of Texas.

Baylor College of Medicine (BCM).







FACTOR YEAR Q
9.091 2006

NLMID: 9421642

PMID: 16858014

ISSN: 1073-449X



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


REVISTA: Am. J. Respir. Crit. Care Med.


NUMERACIÓN: 174(8):928-34


AÑO: 2006


EDITORIAL: American Thoracic Society


AUTORES: Griffith DE., Brown-Elliott BA., Langsjoen B., Zhang Y., Pan X., Girard W., Nelson K., Caccitolo J., Alvarez J., Shepherd S., Willson R., Graviss EA. and Wallace RJ JR.


PARTICIPANTES VISAVET


Julio Álvarez Sánchez

DOI: https://doi.org/10.1164/rccm.200603-450OC


CITA ESTA PUBLICACIÓN:

Griffith DE., Brown-Elliott BA., Langsjoen B., Zhang Y., Pan X., Girard W., Nelson K., Caccitolo J., Alvarez J., Shepherd S., Willson R., Graviss EA. y Wallace RJ JR. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. American Journal of Respiratory and Critical Care Medicine . 174(8):928-34. 2006. (A). ISSN: 1073-449X. DOI: 10.1164/rccm.200603-450OC


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