Optimal aminoglycoside therapy following the sepsis: how much is too much?

Severe sepsis and septic shock are major problems as the result of high rates morbidity and mortality in intensive care units (ICUs). In the presence of septic shock, each hour of delay in the administration of effective antibiotics is associated with a measurable increase in mortality. Aminoglycosides are effective broad-spectrum antibiotics that are commonly used in ICUs for the treatment of life-threatening Gram-negative infections and as a part of empiric therapy for severe sepsis and septic shock. Knowledge of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the antibiotics used for the management of critically ill patients is essential for selecting the antibiotic dosing regimens and improving patient outcome. Volume of distribution (Vd) and clearance (CL) of aminoglycosides in critically ill patients differs from general population and these parameters change considerably during the therapy. Pathophysiological changes during the sepsis alter the pharmacokinetic and pharmacodynamic profile of many drugs (increase in Vd and variable changes in CL have been reported for aminoglycosides during the sepsis), therefore, dosing regimen optimization is necessary for achieving therapeutic goal, and critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels and due to the considerable variation in kinetic parameters, the use of standard doses of aminoglycosides or dosing nomograms is not recommended in these populations.