Glycopeptides in clinical development: pharmacological profile and clinical perspectives.
Vancomycin and teicoplanin are the two glycopeptides currently used in the clinics for the treatment of multiresistant infections by Gram-positive organisms. The development of resistance in enterococci and staphylococci has stimulated the search for new derivatives with improved activity, particularly against strains resistant to conventional derivatives. Three of these, obtained by hemi-synthesis starting from natural compounds, are now in clinical development (oritavancin and telavancin, as derivatives of vancomycin; and dalbavancin, as a derivative of teicoplanin). The presence of a lipophilic tail on these molecules results in them having a prolonged half-life. It also modifies their mode of action, conferring to them a concentration-dependent bactericidal activity. Their spectrum of activity includes methicillin-susceptible or methicillin-resistant staphylococci, penicillin-resistant pneumococci and enterococci (including vancomycin-resistant strains for oritavancin and telavancin). Ongoing clinical studies are evaluating the efficacy and safety of these molecules for the treatment of complicated skin and soft tissue infections and bactereamia, in a once-daily (oritavancin, telavancin) or once-weekly (dalbavancin) scheme of administration. Despite these remarkable properties, the use of these potent molecules should be restricted to severe infections by multiresistant organisms to limit the risk of selection of resistance.
Van Bambeke
Françoise
F
Unité de Pharmacologie Cellulaire et Moléculaire, UCL 7370 Avenue Mounier 73, 1200 Brussels, Belgium. vanbambeke@facm.ucl.ac.be
D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006020:Glycopeptides / Q000737:chemistry / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D016032:Randomized Controlled Trials as Topic; D013329:Structure-Activity Relationship; D017334:Teicoplanin / Q000737:chemistry / Q000494:pharmacology / Q000031:analogs & derivatives; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology / Q000031:analogs & derivatives
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D017334:Teicoplanin; D014640:Vancomycin; C469289:dalbavancin; C100708:oritavancin; C487637:telavancin