Mutational Resistance as the Mechanism of Acquired Drug Resistance to Aminoglycosides and Antibacterial Agents in Mycobacterium fortuitum and Mycobacterium chelonei

Possible mechanisms of drug resistance of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents were investigated. Single-step mutational frequencies were low (generally ⩽ 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, d...