Optimizing aminoglycoside use.

The appearance of new third- and fourth-generation cephalosporins, carbapenems, and fluoroquinolones have decreased the use of aminoglycosides as monotherapy for most gram-negative infections. Historically, aminoglycosides were used in combination with other antibiotics to enhance bacterial killing and improve overall efficacy. However, most studies have failed to demonstrate improved outcomes in patients treated with antibiotic combinations over those receiving monotherapy. Only recently has early combination therapy been associated with reduced mortality in septic shock. This article reviews the pharmacokinetics, pharmacodynamics, and toxicodynamics of aminoglycosides, describing dosing strategies and other effects to improve outcomes in critically ill patients with serious infections.