Lipoglycopeptides

Lipoglycopeptides (dalbavancin, oritavancin and telavancin) are semisynthetic glycopeptides with a lipophilic side chain that anchors them to the bacterial membrane and extends activity. Teicoplanin is a natural glycopeptide with a lipid chain and is sometimes grouped here. Dalbavancin and oritavancin have exceptionally long half-lives, allowing single-dose or two-dose treatment of skin infection and off-label long-acting treatment for bone, joint and endovascular infection.

Mechanism. Binding to the D-alanyl-D-alanine terminus blocks cell wall synthesis; lipophilic chains increase affinity, promote dimerisation and, for oritavancin and telavancin, depolarise the membrane (rapid bactericidal effect). Oritavancin also inhibits transglycosylation of resistant (D-alanyl-D-lactate) precursors.

Pharmacokinetics. All are intravenous, highly protein-bound and slowly eliminated. Terminal half-lives are about 14 days for dalbavancin, about 10 days for oritavancin and 8 hours for telavancin. Poor CSF penetration.

Spectrum. MRSA, MSSA, vancomycin-intermediate S. aureus, streptococci, E. faecalis. Dalbavancin is active against VanB enterococci; oritavancin and telavancin are active against some VanA strains. No Gram-negative activity.

Licensed use. Acute bacterial skin and skin structure infection (all three agents) and, for telavancin, hospital-acquired pneumonia caused by S. aureus when alternatives are unsuitable.

Off-label use. Dalbavancin 1500 mg IV on days 1 and 8 (or 1500 mg every 2 weeks for 2 to 6 doses) is used for osteomyelitis, prosthetic joint infection, endocarditis, and bacteraemia in people who inject drugs or cannot stay in hospital, usually after initial intravenous therapy. Evidence comes from observational studies and small randomised studies and remains limited; infectious diseases advice is needed.

Selection. Useful for outpatient treatment when adherence or access to intravenous therapy is poor. Telavancin is rarely chosen because of toxicity. Availability and cost severely restrict use in East Africa.

Contraindications. Hypersensitivity. Telavancin is contraindicated in pregnancy (boxed risk of foetal harm, with a pregnancy test required beforehand), and with unfractionated heparin within 48 hours after oritavancin because of laboratory interference.

Serious effects. Infusion reactions; nausea; headache; transaminase elevation (dalbavancin, oritavancin); nephrotoxicity and QT prolongation (telavancin); taste disturbance (telavancin); osteomyelitis and tenosynovitis reports with oritavancin; hypersensitivity cross-reaction with vancomycin.

Interactions. Oritavancin: warfarin levels rise, and it can falsely prolong aPTT for up to 120 hours and PT/INR for 12 hours; telavancin affects coagulation tests and interacts with QT-prolonging drugs.

Monitoring. Renal function and liver tests; ECG with telavancin; clinical response over weeks after the final dose because levels persist.

Special groups.

• Renal impairment: dalbavancin 1125 mg once (or 750 mg then 375 mg) when creatinine clearance is under 30 mL/min and not on dialysis; telavancin reduced at clearance under 50 mL/min; oritavancin needs no adjustment.
• Pregnancy: avoid telavancin; data on dalbavancin and oritavancin are limited.
• Breastfeeding: limited data.
• Children: dalbavancin is licensed in some regions for paediatric skin infection with weight-based dosing.