Lipoglycopeptides

Lipoglycopeptides are a subclass of glycopeptide antibiotics distinguished by the addition of a lipophilic side chain to the core glycopeptide structure. This modification enhances antibacterial activity against many Gram-positive pathogens and improves pharmacokinetic properties compared with traditional glycopeptides such as vancomycin.

Mechanistically, lipoglycopeptides bind to the D-alanyl-D-alanine terminus of nascent peptidoglycan precursors, inhibiting cell wall synthesis. The lipophilic side chain facilitates anchoring in the bacterial membrane and can contribute to membrane disruption, promoting rapid bactericidal activity in addition to the blockade of transglycosylation and transpeptidation.

The main approved agents in this class are dalbavancin, oritavancin, and telavancin. They exhibit strong activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and streptococci. Dalbavancin and oritavancin have unusually long half-lives, allowing single-dose or weekly dosing regimens for certain indications, while telavancin has a comparatively shorter half-life.

Clinical use centers on skin and soft tissue infections, particularly acute bacterial skin and skin structure infections, with varying indications among the different agents. The spectrum is predominantly Gram-positive, with limited activity against Gram-negative bacteria. Activity against Enterococcus species, including some vancomycin-resistant strains, varies by agent and organism.

Pharmacokinetics include extended persistence in the body for dalbavancin and oritavancin, renal elimination with dose adjustments as needed, and potential drug interactions. Adverse effects can include infusion reactions, nephrotoxicity (notably with telavancin), QT prolongation, and gastrointestinal symptoms. Resistance can arise through mechanisms affecting the target or cell envelope, but overall resistance to lipoglycopeptides remains less widespread than to many other antibiotic classes.