1. Drugs. 2015 Dec;75(18):2073-95. doi: 10.1007/s40265-015-0505-8.

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative 

Van Bambeke F(1).

Author information: 
(1)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Avenue Mounier 73 B1.73.05, 1200, Brussels,
Belgium. francoise.vanbambeke@uclouvain.be.

Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides 
that exhibit remarkable differences to conventional molecules. While dalbavancin 
inhibits the late stages of peptidoglycan synthesis by mainly impairing
transglycosylase activity, oritavancin and telavancin anchor in the bacterial
membrane by the lipophilic side chain linked to their disaccharidic moiety,
disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps
activity against vancomycin-resistant enterocococci, being a stronger inhibitor
of transpeptidase than of transglycosylase activity. These molecules have potent 
activity against Gram-positive organisms, most notably staphylococci (including
methicillin-resistant Staphylococcus aureus and to some extent
vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant
pneumococci), and Clostridia. All agents are indicated for the treatment of acute
bacterial skin and skin structure infections, and telavancin, for
hospital-acquired and ventilator-associated bacterial pneumonia. While telavancin
is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin 
and dalbavancin allow for infrequent dosing (single dose of 1200 mg for
oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin),
which could be exploited in the future for outpatient therapy. Among possible
safety issues evidenced during clinical development were an increased risk of
developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and
risk of corrected QT interval prolongation (especially in the presence of at-risk
co-medications) with telavancin; and elevation of hepatic enzymes with
dalbavancin. Interference with coagulation tests has been reported with
oritavancin and telavancin. These drugs proved non-inferior to conventional
treatments in clinical trials but their advantages may be better evidenced upon
future evaluation in more severe infections.

PMID: 26603874  [PubMed - in process]