Specific and non-specific resistance to aminoglycosides in Escherichia coli

The turbidimetric responses of a strain of Escherichia coli K12 to gentamicin and tobramycin were investigated. Both agents showed antibacterial activity below the conventionally measured minimum inhibitory concentration, but exposure to such subinhibitory concentrations of either agent generated a bacterial population which was able to grow in previously inhibitory concentrations at a rate equivalent to that of the parent culture. The increase in resistance was non-specific in that both aminoglycosides were equally affected, and was unstable on multiple passage in drug-free broth. The response to tobramycin was unaffected by the presence of an R factor conferring gentamicin resistance, but exposure of the R factor bearing strain to gentamicin caused a concomitant increase in the resistance to tobramycin, apparently by a non-specific adaptive mechanism similar to that observed with the parent strain. It is suggested that prior treatment of a gentamicin-resistant organism with gentamicin (as may occur during blind therapy) may adversely affect the subsequent response to other aminoglycosides.