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

Document Type: Review Paper

Authors

1 Clinical Pharmacy Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

2 1- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2- Gastroenterology and Hepatology Section, Fasa University of Medical Sciences, Fasa, Iran.

3 Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

4 Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

5 Clinical Pharmacy Department, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

6 1- Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2-Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

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.

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