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George Gee Jackson, Valentina T. Lolans, George L. Daikost, The Inductive Role of Ionic Binding in the Bactericidal and Postexposure Effects of Aminoglycoside Antibiotics with Implications for Dosing, The Journal of Infectious Diseases, Volume 162, Issue 2, August 1990, Pages 408–413, https://doi.org/10.1093/infdis/162.2.408
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Abstract
Gram-negative bacilli precooled to 4°C to inactivate energy-dependent drug transport were exposed to an aminoglycoside antibiotic to assess the antibacterial effect of passive ionic binding of drug. Removal of free drug and energizing the cells fiy incubation at 37°C showed the postexposure effect to be bactericidal. The effect was directly related to the amount and concentration of drug in the initial exposure medium proportional to the bacterial density. Binding was nonsaturable at the highest drug:bacteria ratio tested. Elution, exposure ofspheroplasts, and inhibition by divalent cations indicated binding sites in the outer bacterial membrane. Different bacterial species had variable efficiency but similar patterns of binding different aminoglycosides reflecting in vitro susceptibility. The self-promoted postexposure internalization of ionically bound aminoglycoside accounts for the early drug-concentration-dependent rapid bactericidal action ofaminoglycosides. The phenomenon has implications for effective initial dosing with aminoglycoside antibiotics.