Acquired cross resistance to aminoglycosides in gentamicin-sensitive and gentamicin-resistant strains of enterobacteria

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Abstract
The development of non-specific resistance to gentamicin, tobramycin and amikacin was studied in 12 clinical isolates of enterobacteria with various patterns of aminoglycoside resistance. Strains were characterized with respect to MIC [minimal inhibitory concentration], transferability of resistance and possession of acetylating and adenylylating enzymes. An increase in aminoglycoside resistance was induced in 10 strains by a single exposure to the concentration of gentamicin, tobramycin or amikacin immediately below the MIC. Such resistance was nonspecific; all 3 aminoglycosides were affected irrespective of which had been used to induce the increase. Increments in nonspecific aminoglycoside resistance were also evoked by exposure of enterobacteria to changing drug concentrations similar to those achieved in [human] plasma during therapy. When strains already resistant to gentamicin or other aminoglycosides were exposed to therapeutically achievable drug concentrations, no further increase in resistance was observed in most cases. Use of an aminoglycoside to which the organism is resistant, as during blind therapy, will not usually compromise subsequent treatment with related antibiotics. The possible relevance of nonspecific aminoglycoside resistance to therapy is discussed.