Teicoplanin is a glycopeptide antibiotic that is very similar to vancomycin in mechanism of action and antibacterial spectrum. Unlike vancomycin, it can be given intramuscularly as well as intravenously. Teicoplanin has a long half-life (45–70 hours), permitting once-daily dosing. This drug is available in Europe but has not been approved for use in the USA.
Telavancin is a semisynthetic lipoglycopeptide derived from vancomycin. Telavancin is active versus Gram-positive bacteria and has in vitro activity against many strains with reduced susceptibility to vancomycin. Telavancin has two mechanisms of action. Like vancomycin, telavancin inhibits cell wall synthesis by binding to the d-Ala-d-Ala terminus of peptidoglycan in the growing cell wall. In addition, it disrupts the bacterial cell membrane potential and increases membrane permeability. The half-life of telavancin is approximately 8 hours, which supports once-daily intravenous dosing. The drug is approved for treatment of complicated skin and soft tissue infections and hospital-acquired pneumonia at a dose of 10 mg/kg IV daily. Unlike vancomycin therapy, monitoring of serum telavancin levels is not required. Telavancin was associated with substantial nephrotoxicity and concern for increased mortality associated with renal impairment in clinical trials, leading to boxed warnings. It is potentially teratogenic, so administration to pregnant women must be avoided.
Dalbavancin and oritavancin are semisynthetic lipoglycopeptides derived from teicoplanin. Dalbavancin and oritavancin inhibit cell wall synthesis via the same mechanism of action as vancomycin and teicoplanin; oritavancin works by additional mechanisms, including disruption of cell membrane permeability and inhibition of RNA synthesis. Compared with vancomycin, both agents have lower MICs against many Gram-positive bacteria including methicillin-resistant and vancomycin-intermediate S aureus. Dalbavancin is not active against most strains of vancomycin-resistant enterococci (VRE). Oritavancin has in vitro activity against VRE, but its clinical utility in treating VRE infections remains unclear. Both agents have extremely long half-lives of greater than 10 days, which allows for once-weekly intravenous administration. Dalbavancin and oritavancin have been approved for the treatment of skin and soft tissue infections. There are limited clinical data supporting the use of dalbavancin for uncomplicated catheter-associated bloodstream infections, though it is not approved for use in this setting. Dalbavancin was originally approved as a two-dose, once-weekly intravenous regimen (1000 mg infused on day 1 and 500 mg infused on day 8), but a subsequent phase 3 study comparing the two-dose regimen with a single, 1500-mg intravenous dose showed that the single-dose regimen is noninferior. The results of this study allowed for updated labelling, making both dalbavancin and oritavancin appropriate for single-dose treatments for complicated skin and soft tissue infections. A practical difference between the two is the infusion time: dalbavancin can be administered over 30 minutes, while oritavancin must be infused over 3 hours. Neither requires dose adjustment in mild to moderate renal or hepatic impairment, and neither is removed by dialysis.