Glycopeptides: Update on an old successful antibiotic class

The natural product glycopeptides vancomycin and teicoplanin have come to play a significant role in the therapy for Gram-positive bacterial infections. In particular vancomycin is the choice for empiric therapy of these infections primarily due to its activity against and the significance of methicillin-resistant Staphylococcus aureus. While high-level problematic glycopeptide resistance among enterococci was observed initially and continues to increase, the slow creep of vancomycin intermediate susceptibility and the fear of frank resistance among the staphylococci have precipitated increasing work leading to creation of new semisynthetic analogs. These new agents, including dalbavancin and telavancin, are within 1-2 years availability in the clinic. Interestingly, chemical modifications resulting in these second-generation analogs and additional characterization have revealed new mechanisms of antibacterial action, and plasticity regarding additional properties including pharmacokinetics for the drug candidates. The unique beneficial properties of the near term vancomycin replacements, semisynthesis of additional important analogs, and advances in metabolic engineering resulting in novel scaffolds signal a new era for the glycopeptide antibiotics.