Antimicrobial Pharmacokinetic and Pharmacodynamic Issues in the Critically Ill with Severe Sepsis and Septic Shock

In critically ill patients with severe sepsis and septic shock, altered pathophysiology can have a significant influence on pharmacokinetic parameters, particularly Vd and CL, which can then further affect the achievement of pharmacodynamic targets for antimicrobial agents. Failure to achieve pharmacodynamic targets for antimicrobials can result in poor clinical outcomes. Knowledge of the physicochemical properties and PK/PD index associated with maximal activity of an antimicrobial can help clinicians determine if dosage adjustments need to be made. The flow diagrams in Figs. 2 and 3 summarize the effects of pathophysiologic changes on PK/PD parameters for the different hydrophilic and lipophilic antimicrobials and provide suggested dosing recommendations for the different antimicrobial classes. Hydrophilic time-dependent antimicrobials such as beta-lactams may display decreased Cmin as a result of large Vd and/or increased CL, whereas hydrophilic concentration-dependent antimicrobials such as the aminoglycosides may display decreased Cmax as a result of higher Vd in the critically ill patient with sepsis.