title: Glycopeptide antibiotics: back to the future.
abstract: Glycopeptide antibiotics have been a key weapon in the fight against bacterial infections for over half a century, with the progenitors, vancomycin (1) and teicoplanin (2), still used extensively. The increased occurrence of resistance and the effectiveness of these 'last resort' treatments for Gram-positive infections has led to the discovery and clinical development of second generation, semisynthetic lipoglycopeptide derivatives such as telavancin (3), dalbavancin (4) and oritavancin (5), which all possess broader spectra of activity and improved pharmacokinetic properties. Two of these new antibiotics, telavancin (3) and dalbavancin (4), were approved in the past 5 years and the third, oritavancin (5), is awaiting regulatory approval. In this review, the discovery, development and associated resistance of vancomycin (1) and teicoplanin (2), and semi-synthetic glycopeptides, telavancin (3), dalbavancin (4) and oritavancin (5), are detailed. The clinical implications of glycopeptide resistance, especially vancomycin (1), as well as the future prospects for current glycopeptide drugs and the development of new glycopeptides are discussed.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Hansford
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Mark A T
authors.initials: MA
authors.lastname: Blaskovich
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Reena
authors.initials: R
authors.lastname: Halai
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017277:Drug Approval; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006020:Glycopeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides