Lipoglycopeptide Antibiotics
Overview
Lipoglycopeptide antibiotics are semisynthetic derivatives of glycopeptides that have been modified with lipophilic side chains, enhancing their activity against resistant Gram-positive organisms.
Available Agents
- Dalbavancin & Oritavancin
- Telavancin
- Teicoplanin
Mechanism of Action
Lipoglycopeptides have multiple mechanisms of action:
Primary Mechanism
- Inhibition of cell wall synthesis by binding to D-alanyl-D-alanine terminus (similar to glycopeptides)
- Prevents transglycosylation and transpeptidation reactions
Additional Mechanisms
- Membrane depolarization and disruption
- Rapid bactericidal activity against Gram-positive organisms
- Enhanced potency compared to parent glycopeptides
Spectrum of Activity
Enhanced Activity Against
- MRSA (Methicillin-resistant Staphylococcus aureus)
- VRE (Vancomycin-resistant Enterococci) - varies by agent
- Methicillin-resistant coagulase-negative staphylococci
- Streptococcus pneumoniae
- Anaerobic Gram-positive bacteria
Agent-Specific Activity
Dalbavancin
- Excellent activity against staphylococci and streptococci
- Limited activity against VRE
- Long half-life allowing once-weekly dosing
Oritavancin
- Broad activity including VRE
- Rapid bactericidal activity
- Single-dose administration possible
Telavancin
- Dual mechanism (cell wall synthesis inhibition + membrane depolarization)
- Active against MRSA and VRE
- Associated with nephrotoxicity risk
Clinical Applications
Approved Indications
- Complicated skin and soft tissue infections (cSSTI)
- Acute bacterial skin and skin structure infections (ABSSSI)
- Bacteremia (certain agents)
Advantages Over Vancomycin
- Once-daily or once-weekly dosing (improved convenience)
- Enhanced activity against resistant strains
- Reduced monitoring requirements (for some agents)
- Potential for outpatient therapy
Adverse Effects
Common
- Infusion-related reactions (less frequent than vancomycin)
- Nausea and vomiting
- Headache
- Elevated liver enzymes
Agent-Specific Concerns
Telavancin
- Nephrotoxicity (increased risk with other nephrotoxic agents)
- QT prolongation (caution with other QT-prolonging drugs)
Oritavancin
- Interference with coagulation tests (affects PT/INR for up to 24 hours)
Dosing and Administration
Unique Features
- Long half-life allows extended dosing intervals
- Weight-based dosing required for optimal efficacy
- IV administration only (no oral formulation available)
Monitoring
- Renal function monitoring (especially telavancin)
- Liver function tests
- Therapeutic drug monitoring not routinely required
Resistance
Current Status
- Relatively low resistance rates currently
- Cross-resistance with vancomycin uncommon
- Emerging resistance being monitored
Future Considerations
- Important stewardship role in preventing resistance
- Alternative to vancomycin for resistant infections
- Expanding indications under investigation