title: Telavancin shows superior activity to vancomycin with multidrug-resistant Staphylococcus aureus in a range of in vitro biofilm models.
abstract: The activity of telavancin was compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in planktonic culture and biofilms grown using a range of in vitro models. Antibiotic efficacy was determined using 24 clinical isolates, including healthcare-associated (HA)-MRSA, community-associated (CA)-MRSA and isolates with reduced (intermediate) susceptibility to vancomycin (VISA). Activity against biofilms was compared using three models: 96-peg plates, 96-well flat-bottom plates and a flow-cell system. Cell death was evaluated using a metabolic dye and Live/Dead staining. The planktonic minimum inhibitory concentration (MIC) range for telavancin was lower than that for vancomycin (0.06-0.25 mg/l and 0.5-8 mg/l, respectively). Vancomycin (100 × MIC) killed, on average, 59% of cells in HA-MRSA biofilms grown on 96-peg plates, 44% of cells in CA-MRSA biofilms and 26% of cells in VISA biofilms. Telavancin (100 × MIC) killed, on average, 63%, 49% and 41% of cells, respectively. The antibiotics showed similar efficacy against MRSA biofilms but telavancin was more effective against those formed by VISA isolates. In the flow-cell system, antibiotic cell killing was enhanced with both antibiotics, killing up to 80% of biofilm-associated cells. The variance in cell killing displayed when biofilms were grown using different systems highlights the importance of selecting an appropriate model for antimicrobial efficacy tests. The flow-cell system more closely reflects conditions encountered during infection and is possibly more clinically relevant than a 96-well plate system. Despite differences between the models evaluated, telavancin typically demonstrated improved efficacy over vancomycin, indicating the potential value of the agent in the treatment of biofilm-mediated infections caused by S. aureus, especially multidrug-resistant isolates.
authors.affiliation: Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, G4 0BA, Scotland, UK.
authors.forename: K
authors.initials: K
authors.lastname: Smith
authors.forename: C G
authors.initials: CG
authors.lastname: Gemmell
authors.forename: S
authors.initials: S
authors.lastname: Lang
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin