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The pharmacological rationale rests on the concentration-dependent bactericidal activity of aminoglycosides, whereby higher peak-to-MIC ratios enhance killing efficacy, combined with the saturable nature of aminoglycoside uptake into renal tubular and cochlear hair cells: prolonged drug-free intervals between doses may reduce cumulative intracellular drug loading and thereby the potential for organ toxicity ( Meta-analytic evidence consistently supports extended-interval dosing as at least equivalent to multiple daily dosing in efficacy and safety

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