IDENTIFICATION OF MUTATIONS IN 23S RIBOSOMAL-RNA GENE OF CLARITHROMYCIN-RESISTANT MYCOBACTERIUM-INTRACELLULARE

Clarithromycin is a potent macrolide that has been used for treating i nfections with nontuberculous mycobacteria. Pairs of susceptible and r esistant Mycobacterium intracellulare strains were obtained from patie nts with chronic pulmonary M. intracellulare infections undergoing mon otherapy with clarithromycin. Nucleotide sequence comparisons of the p eptidyltransferase region in 23S rRNAs from parental and resistant str ains revealed that in three of six resistant strains, for which the MI C was > 32 mu g/ml, a single base was mutated (Escherichia coli equiva lent, A-2058 --> G, C, or U). As the modification of adenine 2058 by d imethylation is a frequent cause of macrolide resistance in a variety of different bacteria, we suggest that mutation of A-2058 confers acqu ired resistance to clarithromycin in M. intracellulare.