Acquired resistance in Mycobacterium avium complex strains isolated from AIDS patients and beige mice daring treatment with clarithromycin

Clarithromycin has been reported to select clarithromycin resistant mutants of Mycobacterium avium complex (MAC) during treatment with clarithromycin in AIDS patients and beige mice. We selected resistant mutants in vitro at a frequency of 5 x 10(-9). Clarithromycin resistant strains of MAC isolated in AIDS patients and beige mice as well as derivatives selected in vitro had a unique pattern of acquired cross-resistance to macrolides and related antibiotics. In contrast, the pattern of resistance to non-macrolide antibiotics remained unchanged in clarithromycin resistant strains. A dramatic decrease in ribosome affinity for clarithromycin and erythromycin was found in clarithromycin resistant strains, but no mutation was found in the peptidyl domain of the 23S rRNA, indicating that another ribosomal modification is involved.