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.
The Medicines Company, Saint-Laurent, Quebec, Canada.
Francis F
FF
Arhin
Adam
A
Belley
Geoffrey A
GA
McKay
Gregory
G
Moeck
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects; D006020:Glycopeptides / Q000737:chemistry / Q000494:pharmacology*; D055666:Lipopeptides / Q000737:chemistry / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests / Q000379:methods*; D050296:Microbial Viability / Q000187:drug effects
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D055666:Lipopeptides