Specific and non-specific resistance to aminoglycosides in Escherichia coli

SUMMARY 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 con-centrations 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. Gentamicin is now widely used as the treatment of choice for many serious Gram-negative infections. Tobramycin has a similar spectrum of activity to gentamicin (Benveniste and Davies, 1973; Andrews et al., 1973) but is unaffected by some of the bacterial enzymes which inactivate gentamicin. The difference between an adequate therapeutic dosage and toxic dosage of these drugs is small, especially in patients with renal failure (Noone et al., 1974; Mawer et al., 1974). It is therefore desirable that the most efficient way of using them be established. To gain a better understanding of the interaction between drug and bacterium we have investigated the response of a strain of Escherichia coli K12 to various concentrations of gentamicin and tobramycin by continuous turbidimetric monitoring and have attempted to assess the effect of possession of an R factor conferring resistance to gentamicin alone on the responses to gentamicin and tobramycin