1: Drugs.  2004;64(9):913-36.  

Glycopeptide antibiotics: from conventional molecules to new derivatives.

Van Bambeke F, Van Laethem Y, Courvalin P, Tulkens PM.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de
Louvain, Brussels, Belgium.

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.

PMID: 15101783 [PubMed - in process]