EFFECT OF ETHAMBUTOL ON EMERGENCE OF CLARITHROMYCIN-RESISTANT MYCOBACTERIUM-AVIUM COMPLEX IN THE BEIGE MOUSE MODEL

An animal model was developed for studying macrolide-resistant Mycobac terium avium complex (MAC) and to measure the effect of ethambutol on resistance, MAC-infected beige mice were given clarithromycin daily; t he frequency of clarithromycin-resistant MAC after 8 and 12 weeks was 10(-3) and 10(-2), respectively. Combined ethambutol plus clarithromyc in did not increase anti-MAC activity, but clarithromycin-resistant MA C was less frequent (P < .05), The frequency of clarithromycin-resista nt MAC in mice receiving the combination was significantly higher than that in untreated mice, These results are consistent with two human t rials, which showed that adding ethambutol reduced the frequency of cl arithromycin-resistant MAC. Results of the present study suggest that with an initially high level of MAC infection, the addition of ethambu tol may only delay resistance, This mouse test system will be useful f or investigating the influence of the level of MAC infection and the e ffect of other drugs on the frequency of resistant MAC.