Antibiotic pharmacokinetic and pharmacodynamic considerations in patients with kidney disease

Although pharmacokinetic changes occurring in kidney disease are well described, pharmacodynamics in kidney disease is rarely considered. Knowledge of pharmacodynamic principles can allow a clinician to maximize an antibiotic's effectiveness while minimizing adverse effects and antibacterial resistance. An antibiotic's pharmacokinetic and pharmacodynamic profiles should drive dose adjustment decisions in patients with kidney disease. For example, although the half-lives of beta-lactams and aminoglycosides are both prolonged in these patients, beta-lactams exhibit time-dependent antibacterial activity; consequently, maintenance doses should be smaller but given at the same interval. In contrast, aminoglycosides are concentration-dependent antibiotics; hence prolongation of the dosing interval while using larger doses may be advantageous. The timing of drug administration in relation to hemodialysis may be used to achieve specific pharmacodynamic goals. Aminoglycosides given before hemodialysis generate high peaks, whereas subsequent dialytic drug removal minimizes the area under the serum concentration-time curve, potentially decreasing the risk of developing toxicity. Furthermore, new dialysis prescribing patterns (eg, automated peritoneal dialysis, nocturnal dialysis) affect pharmacokinetic and pharmacodynamic parameters in ways not appreciated by clinicians. Studies quantifying the often considerable drug removal with these therapies, as well as efforts to identify pharmacodynamic targets in patients with kidney disease are essential. This paper reviews pharmacodynamic as well as pharmacokinetic issues that should be considered when prescribing antibiotics to treat infections in this population.