Aminoglycosides in hemodialysis patients: is the current practice of post dialysis dosing appropriate?

Aminoglycosides have been widely used in end-stage renal failure patients for the treatment of infections caused by gram-negative bacilli and Staphylococcus aureus. Traditionally, these agents are administered post dialysis to avoid premature dialytic clearance, although no studies have been performed to confirm that this dosing strategy represents the optimal treatment regimen. In recent years, a more complete understanding of the pharmacokinetics-pharmacodynamics of aminoglycosides has led to a global change in clinical practice from multiple to once-daily dosing in patients with normal renal function with the aim of providing intermittent pulses to maximize the peak concentration relative to overall drug exposure. These same considerations strongly support administration of aminoglycosides before, rather than after, hemodialysis. This study will review the key pharmacokinetic/pharmacodynamic considerations in aminoglycoside dosing, the relationship between serum aminoglycoside concentrations and efficacy/toxicity, the influence of renal function and hemodialysis on aminoglycoside pharmacokinetics/pharmacodynamics, and the mounting population pharmacokinetic and clinical study evidence supporting a paradigm shift in aminoglycoside dosing from post dialysis to predialysis.