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J Infect Dis. 1990 Aug;162(2):408-13.

The inductive role of ionic binding in the bactericidal and postexposure effects of aminoglycoside antibiotics with implications for dosing.

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1
Department of Medical Microbiology, London Hospital Medical College, United Kingdom.

Abstract

Gram-negative bacilli precooled to 4 degrees 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 by incubation at 37 degrees 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 of spheroplasts, 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 of aminoglycosides. The phenomenon has implications for effective initial dosing with aminoglycoside antibiotics.

PMID:
2115554
[Indexed for MEDLINE]
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