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Clarithromycin is a potent macrolide that has been used for treating infections with nontuberculous mycobacteria. Pairs of susceptible and resistant Mycobacterium intracellulare strains were obtained from patients with chronic pulmonary M. intracellulare infections undergoing monotherapy with clarithromycin. Nucleotide sequence comparisons of the peptidyltransferase region in 23S rRNAs from parental and resistant strains revealed that in three of six resistant strains, for which the MIC was >32 ,ug/ml, a single base was mutated (Escherichia coli equivalent, A-2058 ->G, C, or U). As the modification of adenine 2058 by dimethylation is a frequent cause of macrolide resistance in a variety of different bacteria, we suggest that mutation of A-2058 confers acquired resistance to clarithromycin in M. intracellulare.Slowly growing mycobacteria, including Mycobacterium kansasii, M. marinum, M. simiae, M. scrofulaceum, M. szulgai, M. nonchromogenicum, M. intracellulare, and M. avium complex (MAC), have been implicated in various types of human diseases, including skin and soft tissue infections and pulmonary disease. Notably, a common complication in patients with late-stage AIDS is disseminated infection with MAC. In relation to the CD4 cell count, the prevalences of disseminated MAC infection in these patients were reported to be 21% at 1 year and 43% at 2 years following the diagnosis of AIDS (17).Recently, new macrolides, including clarithromycin, roxithromycin, and azithromycin, were synthesized. The in vitro evaluations of these new macrolides as potential therapeutic agents for mycobacterial infections have demonstrated that clarithromycin in particular has activity against isolates of nontuberculous mycobacteria (1, 2, 9). A double-blind clinical trial showed that within 6 weeks, monotherapy with clarithromycin produced a dramatic decrease in the number of viable bacteria in the blood of patients with AIDS and disseminated MAC infection (3). However, it was simultaneously noted that monotherapy with clarithromycin can lead to drug resistance (21).Macrolides are bacteriostatic antibiotics which inhibit the peptidyltransferase region of the 50S ribosomal subunit (for a review, see reference 6). A few years after the introduction of erythromycin for therapy, resistance of Staphylococcus aureus to this drug emerged. For these resistent strains, simultaneous resistance to other macrolides, to lincomycin, and to streptogramin B antibiotics was noted. This is the so-called MLS phenotype (29). Although the exact mechanism of translational inhibition by these drugs is still undetermined, a peptidyltransferase center in a small region of 23S rRNA has been identified by mapping resistance to several transferase inhibitors. In particular, the Escherichia coli equivalent A-2058 (511) 532-4366. 381 implicated in peptidyl transfer (18). The MLS cross-resistance phenotype due to modification of the drug target is widely distributed and has been detected in a number of grampositive and gram-negative bacteria. Clinically ac...

Previous studies of Mycobacterium fortuitum identified isolates that did not fit its two recognized biovariants. Eighty-five clinical isolates of this group, the "third biovariant complex", were evaluated. They represented 16% of 410 isolates of M. fortuitum submitted to a Texas laboratory and 22% of 45 isolates in Queensland, Australia. Most infections (76%) involved skin, soft tissue, or bone and occurred after metal puncture wounds or open fractures. Isolates differed from biovar fortuitum in resistance to pipemidic acid and use of mannitol and inositol as carbon sources. Two subgroups were present, and examples were deposited in the American Type Culture Collection. Isolates were resistant to doxycycline and one-third were resistant to cefoxitin. All were susceptible to amikacin, ciprofloxacin, sulfamethoxazole, and imipenem. Surgical debridement combined with drug therapy based on in vitro susceptibilities resulted in cures of cutaneous disease or osteomyelitis. DNA homology studies are needed to determine the taxonomic status of these organisms.