Pharmacodynamics of Lipoglycopeptides

Abstract

Telavancin, dalbavancin, and oritavancin are lipoglycopeptide anti-infective agents with a broad in vitro spectrum against gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). The research and development programs of these agents have been challenging and have resulted in the generation of various pharmacokinetic and pharmacodynamic data over the past 10–15 years. All of the lipoglycopeptide agents exhibit concentration-dependent bactericidal activity with the ratio of unbound area-under-the-curve to minimum inhibitory concentration (fAUC/MIC) best predicting antibacterial efficacy in vitro and in vivo. The pharmacokinetic and exposure-response characteristics support the recommended once-daily dosing regimen for telavancin, a two-dose regimen for dalbavancin (1000 mg followed 1 week later by a 500 mg dose) and a novel single-dose regimen for oritavancin (1200 mg). Further research and clinical experiences with these lipoglycopeptide agents are needed in order to expand their use to other types of invasive infections caused by MRSA.