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

The Journal of Infectious Diseases
Luiz E BermudezS Young Lowell

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 out...Continue Reading

References

Sep 28, 1989·The New England Journal of Medicine·D S PrinceJ E Fish
Jul 1, 1993·Clinical Microbiology Reviews·C B InderliedL E Bermudez
Jun 18, 1996·Annals of the New York Academy of Sciences·S J Blumenthal
Apr 1, 1996·Clinical Microbiology Reviews·J O Falkinham
Feb 4, 1998·Antimicrobial Agents and Chemotherapy·L E BermudezL S Young
Aug 7, 1998·Frontiers in Bioscience : a Journal and Virtual Library·A M CooperI M Orme
Sep 10, 1998·American Journal of Respiratory and Critical Care Medicine·K KuboS Sone
Oct 14, 1998·American Journal of Respiratory and Critical Care Medicine·R J WallaceD E Griffith
Oct 10, 2002·Clinics in Chest Medicine·Deborah L Ebert, Kenneth N Olivier
Nov 25, 2004·Antimicrobial Agents and Chemotherapy·George CarterLuiz E Bermudez
Jan 5, 2006·Applied and Environmental Microbiology·Yoshitaka YamazakiLuiz E Bermudez
Mar 4, 2006·American Journal of Respiratory and Critical Care Medicine·Phung K LamAntonino Catanzaro
Jul 22, 2006·American Journal of Respiratory and Critical Care Medicine·David E GriffithRichard J Wallace
Feb 6, 2007·American Journal of Respiratory and Critical Care Medicine·David E GriffithUNKNOWN Infectious Disease Society of America
Feb 14, 2007·Antimicrobial Agents and Chemotherapy·Luiz E BermudezLowell S Young

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Citations

Nov 13, 2015·American Journal of Respiratory Cell and Molecular Biology·Kevin WinthropIlhem Messaoudi
Jun 15, 2010·Pulmonary Pharmacology & Therapeutics·Emmet E McGrath, Paul B Anderson
Jun 5, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·João P SilvaF Miguel Gama

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