The efficacy of clarithromycin and the bicyclolide EDP-420 against Mycobacterium avium in a mouse model of pulmonary infection.

TitleThe efficacy of clarithromycin and the bicyclolide EDP-420 against Mycobacterium avium in a mouse model of pulmonary infection.
Publication TypeJournal Article
Year of Publication2008
AuthorsBermudez LE, Motamedi N, Kolonoski P, Chee C, Baimukanova G, Bildfell RJ, Wang G, Phan LT, Lowell YS
JournalThe Journal of infectious diseases
Volume197
Issue11
Pagination1506-10
Date Published2008 Jun 1
ISSN0022-1899
KeywordsAnimals, Antitubercular Agents, Bridged Compounds, Clarithromycin, Female, Lung, Macrolides, Mice, Mice, Inbred C57BL, Mycobacterium avium, Tuberculosis, Pulmonary
Abstract

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.

DOI10.1086/587906
Alternate JournalJ. Infect. Dis.