Resistance of bacteria to aminoglycoside antibiotics is determined by several mechanisms which include alteration of the target site, enzymatic inactivation of the drug, or establishment of a permeability barrier to the drug. When natural (clinical) isolates of resistant organisms are compared to laboratory-derived resistant strains, it is apparent that the most important mechanism of resistance in natural isolates is inactivation due to the presence of R-factors. Resistance is more likely to occur via a mutational event in laboratory strains.
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J. Davies (1971) studied this question.