Single daily dose therapy with aminoglycosides

Abstract

Although aminoglycosides are generally infused every 8 or 12 h, recent data suggest that administration of the total daily dose every 24 h may reduce the risk of oto- and nepbrotoxicity and improve efficacy. Aminoglycosides kill bacteria in a dose-dependent manner (i.e. the higher the drug level, the more rapid and complete the bactericidal effect), and exert a post-antibiotic effect (delay in regrowth after the drug concentration falls below its minimum inhibitory concentration for the strain). Moreover, survivors after initial aminoglycoside exposure are temporarily relatively insensitive to the drug, so longer interdose intervals allow recovery of greater sensitivity. Thus, dosing to achieve higher peak drug levels less often would seem desirable. In several animal models of infection, greater efficacy and less oto- and nephrotoxicity have been associated with once daily dosing of aminoglycosides. Several clinical studies have indicated the importance of high peak serum aminoglycoside levels for efficacy. Limited studies of once daily dosing of these drugs in man have suggested that it is at least as favourable as conventional dosing. Nonetheless, despite the obvious advantages of cost and convenience and the theoretical and experimental indication that once daily dosing is advantageous, we need to test this concept in the clinical situation. Large prospective, randomized, double-blind, comparative studies of once daily and conventional dosing regimens in the treatment of various infections in different patient populations are required.