Characterization of the In Vitro Activity of Novel Lipoglycopeptide Antibiotics

The increasing incidence of antibiotic resistance in human pathogens is of significant concern. Resistance to the widely‐used and highly effective glycopeptide antibacterial agent vancomycin, which has been in clinical use for over half a century, has emerged in staphylococci and enterococci. This has spurred the development of newer glycopeptide agents, some of which show activity against vancomycin‐resistant organisms. The newer agents currently being developed contain lipophilic side‐chains, which distinguish them from vancomycin; as such, they are categorized as lipoglycopeptides. Oritavancin, telavancin, and dalbavancin are lipoglycopeptides in late‐stage development to combat Gram‐positive bacteria including methicillin‐resistant Staphylococcus aureus(MRSA) and vancomycin‐resistant enterococci. This unit describes methods that may be used to assess the in vitro activities of lipoglycopeptides. The methods include susceptibility assays, time‐kill and time‐kill‐synergy assays, inhibition of synthesis of macromolecules, membrane perturbation assays, and measurement of activity against biofilms. Curr. Protoc. Microbiol. 16:17.1.1‐17.1.22. © 2010 by John Wiley & Sons, Inc.