Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections

Abstract

Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs). It is active against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and minimum inhibitory concentrations (MICs) are consistently <0.125 µg/ml, much lower than most other anti-MRSA agents. Dalbavancin possesses an extended half-life of over 1 week, allowing an initial dose of 1000 mg followed by 500 mg 1 week later to complete a course of therapy for ABSSSI. It is approximately 95% protein bound and is widely distributed throughout the body, achieving concentrations similar to plasma levels in numerous tissues. Against MRSA, dalbavancin is 4–8 times more potent than vancomycin in vitro, and limited data suggest it possesses activity against MRSA with reduced susceptibility to vancomycin such as hVISA and VISA. Dalbavancin also possesses in vitro activity against streptococci and enterococci, although activity against vancomycin-resistant enterococci is lacking. In phase 3 ABSSSI studies, dalbavancin demonstrated similar activity to vancomycin and provides a more convenient dosing regimen. Limited phase 2 data suggest dalbavancin also possesses activity in catheter-related bloodstream infections. Potential further therapeutic uses include conditions that require long-term treatment such as osteomyelitis and infective endocarditis, although data are currently lacking. The extended half-life of dalbavancin, along with its in vitro activity against gram-positive organisms with reduced susceptibility to other anti-MRSA antibiotics, suggest it could have an exciting clinical role going forward.