Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

Abstract

The treatment of sepsis remains a significant challenge and is the cause of high mortality and morbidity. The pathophysiological alterations that are associated with sepsis can complicate drug dosing. Critical care patients often have capillary leak, increased cardiac output and altered protein levels which can have profound effects on the volume of distribution (Vd) and clearance (Cl) of antibacterial agents, both of which may affect the pharmacokinetics (PK) / pharmacodynamics (PD) of the drug. Along with antibacterial factors such as the hydrophilicity and its kill characteristics and the susceptibility and site of action of the microorganism, different dosing and administration strategies may be needed for the different drug classes. In conclusion, developing dosing and administration regimes of antibacterials that adhere to PK/PD principles increase antibacterial exposure. Tailoring therapy to the individual patient combined with TDM may contribute to improved clinical efficacy and contain the spread of resistance.