Bermudez L E, Nash K A, Petrofsky M, Young L S, Inderlied C B
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115, USA.
J Infect Dis. 1996 Dec;174(6):1218-22. doi: 10.1093/infdis/174.6.1218.
An animal model was developed for studying macrolide-resistant Mycobacterium avium complex (MAC) and to measure the effect of ethambutol on resistance. MAC-infected beige mice were given clarithromycin daily; the frequency of clarithromycin-resistant MAC after 8 and 12 weeks was 10(-3) and 10(-2), respectively. Combined ethambutol plus clarithromycin did not increase anti-MAC activity, but clarithromycin-resistant MAC was less frequent (P < .05). The frequency of clarithromycin-resistant MAC in mice receiving the combination was significantly higher than that in untreated mice. These results are consistent with two human trials, which showed that adding ethambutol reduced the frequency of clarithromycin-resistant MAC. Results of the present study suggest that with an initially high level of MAC infection, the addition of ethambutol may only delay resistance. This mouse test system will be useful for investigating the influence of the level of MAC infection and the effect of other drugs on the frequency of resistant MAC.
为研究大环内酯类耐药鸟分枝杆菌复合体（MAC）并测定乙胺丁醇对耐药性的影响，建立了一种动物模型。对感染MAC的米色小鼠每日给予克拉霉素；8周和12周后克拉霉素耐药MAC的频率分别为10^(-3)和10^(-2)。乙胺丁醇联合克拉霉素并未增强抗MAC活性，但克拉霉素耐药MAC的频率较低（P < 0.05）。接受联合用药的小鼠中克拉霉素耐药MAC的频率显著高于未治疗小鼠。这些结果与两项人体试验一致，这两项试验表明添加乙胺丁醇可降低克拉霉素耐药MAC的频率。本研究结果表明，在最初MAC感染水平较高时，添加乙胺丁醇可能只会延迟耐药性的产生。这种小鼠试验系统将有助于研究MAC感染水平的影响以及其他药物对耐药MAC频率的作用。
