Drugs

, Volume 64, Issue 9, pp 913–936 | Cite as

Glycopeptide Antibiotics

from Conventional Molecules to New Derivatives
  • Françoise Van Bambeke
  • Yves Van Laethem
  • Patrice Courvalin
  • Paul M. Tulkens
Leading Article

Abstract

Vancomycin and teicoplanin are still the only glycopeptide antibiotics available for use in humans. Emergence of resistance in enterococci and staphylococci has led to restriction of their use to severe infections caused by Gram-positive bacteria for which no other alternative is acceptable (because of resistance or allergy). In parallel, considerable efforts have been made to produce semisynthetic glycopeptides with improved pharmacokinetic and pharmacodynamic properties, and with activity towards resistant strains. Several molecules have now been obtained, helping to better delineate structure-activity relationships. Two are being currently evaluated for skin and soft tissue infections and are in phases II/ III. The first, oritavancin (LY333328), is the 4′-chlorobiphenylmethyl derivative of chloroeremomycin, an analogue to vancomycin. It is characterised by: i) a spectrum covering vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and to some extent glycopeptide-intermediate S. aureus (GISA); ii) rapid bactericidal activity including against the intracellular forms of enterococci and staphylococci; and iii) a prolonged half-life, allowing for daily administration. The second molecule is dalbavancin (BI397), a derivative of the teicoplanin analogue A40926. Dalbavancin has a spectrum of activity similar to that of oritavancin against vancomycin-sensitive strains, but is not active against VRE. It can be administered once a week, based on its prolonged retention in the organism. Despite these remarkable properties, the use of these potent agents should be restricted to severe infections, as should the older glycopeptides, with an extension towards resistant or poorly sensitive bacteria, to limit the risk of potential selection of resistance.

Keywords

Minimum Inhibitory Concentration Vancomycin Glycopeptide Teicoplanin Glycopeptide Antibiotic 

Notes

Acknowledgements

F. Van Bambeke is Chercheur Qualifié of the Belgian Fonds National de la Recherche Scientifique. The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Françoise Van Bambeke
    • 1
  • Yves Van Laethem
    • 2
  • Patrice Courvalin
    • 3
  • Paul M. Tulkens
    • 1
  1. 1.Unité de Pharmacologie cellulaire et moléculaireUniversité Catholique de LouvainBrusselsBelgium
  2. 2.Service des Maladies InfectieusesHôpital Saint PierreBrusselsBelgium
  3. 3.Unité des Agents AntibactériensInstitut PasteurParisFrance

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