Alternative Dosing Strategy for Aminoglycosides: Impact on Efficacy, Nephrotoxicity, and Ototoxicity

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Abstract
Accumulating evidence suggests that the therapeutic margin of aminoglycoside therapy may be improved by manipulation of dosing strategy. Recent understanding of concentration-dependent bactericidal activity and postantibiotic effect argues that the aminoglycosides may be administered in larger doses and at longer dosing intervals than currently recommended without compromising efficacy. Preliminary clinical experience suggests that once-daily regimens are as efficacious as conventional intermittent injections in the treatment of gram-negative infections including urinary tract infections, cystic fibrosis, and bacteremia in nonneutropenic patients. The transient, high peak serum concentrations achieved in once-daily dosing have not been associated with excessive nephrotoxicity or ototoxicity thus far. Decreased accumulation in renal cortex as a result of saturable renal uptake after the single daily dose may even reduce the incidence or severity of renal damage. Further studies on more patients are required to substantiate these preliminary findings.