Optimal Aminoglycoside Therapy Following the Sepsis: How Much Is Too Much?

Abstract

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