The Use of Extended-Interval Aminoglycoside Dosing Strategies for the Treatment of Moderate-to-Severe Infections Encountered in Critically Ill Surgical Patients

Abstract

Background: Extended-interval dosing strategies have been developed to exploit the concentration-dependent bactericidal activity and time-dependent host toxicity associated with aminoglycoside the therapy. The ability of published extended-interval dosing nomograms to achieve optimal pharmacodynamic endpoints may be limited in certain critically ill surgical patients.

Methods: Review of pertinent English language literature. Presentation of descriptive, graded recommendations for extended-interval aminoglycoside dosing in critically ill surgical patients.

Results: Aminoglycoside dosing considerations in critically ill surgical patients should attempt to maximize the bacterial and host pharmacodynamic attributes of these agents. Empirically, extended-interval aminoglycoside doses proposed by published nomograms are reasonable for most patients; however, because of clinically meaningful variations in aminoglycoside pharmacokinetics, routine use of published extended-interval aminoglycoside dosing nomograms to determine an appropriate dosage interval is discouraged in many critically ill surgical patients. Critically ill surgical patients receiving extended-interval aminoglycoside dosages should undergo individualized pharmacokinetic analysis to characterize efficiently and more effectively plasma concentration-to-bacterial minimum inhibitory concentration (MIC) relationships and determine an appropriate dosing interval, considering site and severity of infection, plasma clearance, and the apparent post-antibiotic effect.

Conclusions: The use of extended-interval aminoglycoside dosage regimens in critically ill surgical patients should be based on pharmacodynamic endpoints and patient-specific pharmacokinetic assessment.