title: Effect of ethambutol on emergence of clarithromycin-resistant Mycobacterium avium complex in the beige mouse model.
abstract: 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.
authors.affiliation: Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Bermudez
authors.forename: K A
authors.initials: KA
authors.lastname: Nash
authors.forename: M
authors.initials: M
authors.lastname: Petrofsky
authors.forename: L S
authors.initials: LS
authors.lastname: Young
authors.forename: C B
authors.initials: CB
authors.lastname: Inderlied
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use*; D005260:Female; D005798:Genes, Bacterial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016297:Mutagenesis, Site-Directed; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D013154:Spleen / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D012338:RNA, Ribosomal, 23S; D004977:Ethambutol; D017291:Clarithromycin