title: Mutational resistance as the mechanism of acquired drug resistance to aminoglycosides and antibacterial agents in Mycobacterium fortuitum and Mycobacterium chelonei. Evidence is based on plasmid analysis, mutational frequencies, and aminoglycoside-modifying enzyme assays.
abstract: Possible mechanisms of drug resistance of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents were investigated. Single-step mutational frequencies were low (generally less than or equal to 10(-7] for cefoxitin, doxycycline, erythromycin, and sulfamethoxazole and relatively high (10(-4) to 10(-7] for kanamycin and amikacin. Aminoglycoside-susceptible strains of both species contained an aminoglycoside acetyltransferase (3)-III or IV. No additional enzymes were seen with laboratory or clinically acquired aminoglycoside resistance. Plasmids of several sizes were present in some susceptible isolates of both species, but acquired resistance was not associated with a change in the apparent size or number of these plasmids. Isolates with acquired resistance to amikacin were resistant to the other 2-deoxystreptamine aminoglycosides but showed little or no change in minimal inhibitory concentrations to streptomycin, suggesting either a difference in cellular uptake between the 2 groups of drugs or, more likely, different binding sites on the ribosome. In 59 patients treated with 63 courses of therapy with a single agent for 1 month or longer, the development of resistance was observed only twice (3%). Both isolates had high mutational frequencies (10(-4) and 10(-5]. These studies support mutational resistance as the mechanism of acquired resistance to antibacterial agents in M. fortuitum and M. chelonei.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D009164:Mycobacterium Infections / Q000188:drug therapy; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy; D009170:Nontuberculous Mycobacteria / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D011815:R Factors
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents