Lipoglycopeptides

Lipoglycopeptides are not absorbed orally and are available only as IV formulations. Lipoglycopeptides penetrate well into pulmonary epithelial lining fluid and skin blisters.

Telavancin has a half-life of 7 to 9 hours and a postantibiotic effect of about 4 hours. Dalbavancin has a prolonged half life of 204 hours, and oritavancin has a prolonged half-life of 245 to 393 hours; thus, single-dose regimens with these drugs are possible.

Telavancin is excreted by the kidneys, so the dose must be adjusted in patients with renal insufficiency.

Lipoglycopeptides are broadly active against gram-positive bacteria, including

• Streptococci

• Enterococcus faecalis

• Enterococcus faecium

• Staphylococcus aureus, including S. aureus that is methicillin-resistant or vancomycin–intermediate-resistant

Oritavancin is active against vancomycin-resistant enterococci (VRE) strains that harbor the vanA gene; dalbavancin and telavancin are not. Dalbavancin, oritavancin, and telavancin have activity against vanB VRE. All three lipoglycopeptides are active against Staphylococcus aureus and Staphylococcus epidermidis regardless of their susceptibility to methicillin. Only oritavancin is active against vancomycin-resistant S. aureus.

Telavancin is used for complicated skin and skin structure infections as well as for hospital-acquired and ventilator-acquired bacterial pneumonia caused by sensitive isolates of S. aureus.

The long-acting lipoglycopeptides dalbavancin and oritavancin are used to treat acute bacterial skin and skin structure infections but are still being studied as treatment for more invasive infections.

Lipoglycopeptides are contraindicated in patients who are allergic to them. They should be used with care in patients who are allergic to vancomycin or other glycopeptides because cross-reactivity is possible.

Lipoglycopeptides have had some adverse effects on fetal development in animals; safety data in pregnant women are limited. Lipoglycopeptides should be used during pregnancy only if the potential benefit to the patient outweighs the potential risk to the fetus.

There are no data regarding excretion in breast milk in humans, but lipoglycopeptides are known to be excreted in the breast milk of rats.

Common adverse effects of lipoglycopeptides include

• Nausea and vomiting

• Taste disturbance

• Foamy urine

Telavancin and oritavancin may falsely increase values on coagulation tests (prothrombin time/partial thromboplastin time [PT/PTT]) for a period of time. Therefore, blood for these tests should be drawn before these antibiotics are given. Dalbavancin does not artificially prolong PT or PTT. Telavancin interferes with urine protein assays.

Significant adverse effects include

• Increased mortality in patients with pre-existing moderate/severe renal impairment (creatinine clearance ≤ 50 mL/minute) who were treated with telavancin for hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia versus vancomycin

• A histamine-mediated pruritus and flushing of the face, neck, and shoulders, similar to vancomycin infusion reaction.

• Nephrotoxicity, which may occur more often with telavancin than with vancomycin but has not been associated with dalbavancin or oritavancin

• With telavancin, QTc prolongation

Nephrotoxicity with telavancin is more likely in patients with known kidney dysfunction, disorders that predispose to kidney dysfunction (eg, diabetes, hypertension, heart failure), or use of potentially nephrotoxic drugs. Renal function should be assessed before starting the drug and monitored at least every 48 to 72 hours.

Pruritus and flushing associated with rapid infusion of lipoglycopeptides can be prevented by infusing at a slower rate if the patient shows signs of flushing and pruritis.

QTc prolongation occurred in healthy subjects in the clinical trials of telavancin; thus, telavancin should be used with caution or not be used in patients taking drugs that prolong the QT interval. Telavancin should not be used in patients with congenital long QT syndrome, known QTc prolongation, uncompensated heart failure, or severe left ventricular hypertrophy (patients with these disorders were excluded from the clinical trials).

Dalbavancin doses should be reduced in patients with creatinine clearance < 30 mL/minute; clinicians should use 1125 mg for single-dose regimens or 750 mg once followed by 375 mg 1 week later. No dosage adjustment is recommended for patients who are regularly receiving hemodialysis.

Oritavancin does not appear to require renal dose adjustment, but adequate studies to support a recommendation for patients with renal failure have not been done.

Telavancin dosing is based on creatinine clearance:

• Creatinine clearance > 50 mL/minute: 10 mg/kg IV every 24 hours

• Creatinine clearance 30 to 50 mL/minute: 7.5 mg/kg every 24 hours

• Creatinine clearance 10 to < 30 mL/minute: 10 mg/kg every 48 hours

• Creatinine clearance < 10 mL/minute: Data limited, no recommendations available