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

TheMycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen forM. avium complex infection has not been established. Clarithromycin is accepted as the corner-stone drug for treatment ofM. avium lung disease; however, good model systems, especially animal models, are needed to evalu-ate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (com-paring BALB/c, C57BL/6, nude, and beige mice) ofM. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible toM. avium infection 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 thanmoxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithro-mycin-containing regimens are the most effective forM. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. Pulmonary disease due to nontuberculous mycobacteria(NTM) is on the rise worldwide (1, 2), and in several areas, including theUnited States andCanada, the incidence rate of such disease is higher than that of tuberculosis (3, 4). The most com