Lipoglycopeptide

Lipoglycopeptide is a class of glycopeptide antibiotics that incorporate a lipid (lipophilic) side chain attached to the glycopeptide core. This structural feature distinguishes them from classical glycopeptides such as vancomycin and teicoplanin and contributes to their enhanced activity and distinct pharmacokinetic properties. Representative agents include dalbavancin, oritavancin, and telavancin, all of which are approved for human use in various indications.

The mechanism of action combines the traditional glycopeptide effect with membrane interactions. Lipoglycopeptides bind to the D-Ala-D-Ala terminus of lipid II peptidoglycan precursors, inhibiting transglycosylation and transpeptidation, which disrupts cell wall synthesis. The lipophilic side chain can also anchor the drug to the bacterial membrane and, in some cases, perturb membrane integrity, contributing to bactericidal activity against many Gram-positive pathogens.

Spectrum-wise, lipoglycopeptides have potent activity primarily against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and various streptococci. Activity against Gram-negative organisms is limited due to permeability barriers. Clinically, dalbavancin and oritavancin are approved mainly for acute bacterial skin and skin-structure infections, with regimens designed for outpatient convenience. Telavancin is approved for complicated skin infections and has an additional indication for hospital-acquired pneumonia in some regions.

Pharmacokinetically, these agents typically have long half-lives, enabling extended or single-dose regimens with IV administration. Dalbavancin and oritavancin support infrequent dosing, while telavancin is usually given on a daily schedule for a defined course. Safety concerns include infusion-related reactions, nephrotoxicity (particularly with telavancin), and fetal toxicity risk in pregnancy. Resistance can arise through modifications that reduce binding to the D-Ala-D-Lac motif, and cross-resistance with other glycopeptides can occur.

In summary, lipoglycopeptides offer targeted, long-acting therapy against select Gram-positive infections, with unique pharmacokinetics that enable simplified dosing but require careful safety monitoring.