Open AccessThe Efficacy of Clarithromycin and the Bicyclolide EDP‐420 againstMycobacterium aviumin a Mouse Model of Pulmonary Infection
Author(s) -
Luiz E. Bermudez,
Nima Motamedi,
Peter Kolonoski,
Chris Chee,
Gail Baimukanova,
Robert J. Bildfell,
Guoqiang Wang,
Ly T. Phan,
Lowell S. Young
Publication year - 2008
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/587906
Subject(s) - clarithromycin , mycobacterium avium complex , medicine , lung , mycobacterium avium intracellulare infection , pulmonary disease , lung disease , mycobacterium , disease , respiratory disease , immunology , pathology , tuberculosis , helicobacter pylori
Lung disease caused by Mycobacterium avium complex (MAC) is increasing in prevalence. MAC disease occurs in patients with chronic preexisting obstructive pulmonary diseases but is also diagnosed in individuals with no history of lung pathology or identifiable immune defect. Histologically, the disease is characterized by either the development of nodular granulomatous lesions in the peribronchial region or cavitary peripheral disease in smokers. Response to long-term treatment is poor. Limited comparative-efficacy data on treatment exist. A model that resembles nodular MAC disease was established in C57 (bg+/bg+) mice infected intranasally. Therapy with clarithromycin, a compound commonly used to treat MAC disease, was evaluated in parallel with treatment using a new bicyclolide, EDP-420, that achieves high levels of intrapulmonary concentrations. Although clarithromycin administered daily resulted in a reduction in the bacterial load in the lung, EDP-420 administered either daily or twice a week was significantly more effective. These results suggest that this animal model can be used to evaluate novel regimens against MAC disease and that compounds with high concentration in the lung might have a significant impact on the outcome of MAC lung disease.