Extended-Interval Dosing of Aminoglycoside Antibiotics in Critically Ill Patients

Abstract

Although aminoglycosides remain an essential part of therapy of severe gram-negative infections in critically ill patients, the use of extended-interval aminoglycoside dosing (EIAD) in this population is highly controversial. The rationale for EIAD is based on major pharmacodynamic characteristics of the aminoglycosides, which include concentration-dependent bactericidal effects, postantibiotic effect, and adaptive resistance. Alterations in the pharmacokinetics of aminoglycosides in the critically ill have been well documented, including changes in both drug distribution and elimination. These pharmacokinetic alterations may prevent critically ill patients from realizing the potential benefits of EIAD by reducing serum concentrations achieved by recommended EIAD regimens and may perhaps place patients at risk of therapeutic failure. Although numerous studies of EIAD have been conducted, there is a lack of data specifically concerning the efficacy and safety of EIAD in the critically ill. The most appropriate methods for monitoring EIAD in this population are also not clearly established. There are thus many questions regarding the suitability of EIAD in the critically ill. This article briefly reviews the rationale for EIAD and data related to the pharmacokinetics, efficacy, safety, and clinical monitoring of EIAD in critically ill patients. Considerations and recommendations for use of EIAD in the critically ill are provided.