Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations

Abstract

ABSTRACTTheMycobacterium aviumcomplex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen forM. aviumcomplex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment ofM. aviumlung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) ofM. aviuminfection and to assess the anti-M. aviumactivity of single and combination drug regimens,in vitro,ex vivo, and in mice.In vitro, clarithromycin and moxifloxacin were most active againstM. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible toM. aviuminfection than the other mouse strains tested, but the impact of treatment was most clearly seen inM. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective forM. aviuminfection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy.