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Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

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Abstract

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.

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Acknowledgments

F. Van Bambeke is Maître de Recherches from the Belgian du Fonds de la Recherche Scientifique.

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  1. Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Avenue Mounier 73 B1.73.05, 1200, Brussels, Belgium

    Françoise Van Bambeke

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F. Van Bambeke received research grants from Targanta Therapeutics (now The Medicines Company), and Theravance for the performance of in vitro work with oritavancin and telavancin, respectively (most of the corresponding references cited in the present paper).

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Van Bambeke, F. Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review. Drugs 75, 2073–2095 (2015). https://doi.org/10.1007/s40265-015-0505-8

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