title: The activity of vancomycin against heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus explored using an in vitro pharmacokinetic model.
abstract: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.
authors.affiliation: Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS1 5NB, UK.
authors.forename: J
authors.initials: J
authors.lastname: Turner
authors.forename: R A
authors.initials: RA
authors.lastname: Howe
authors.forename: M
authors.initials: M
authors.lastname: Wootton
authors.forename: K E
authors.initials: KE
authors.lastname: Bowker
authors.forename: H A
authors.initials: HA
authors.lastname: Holt
authors.forename: V
authors.initials: V
authors.lastname: Salisbury
authors.forename: P M
authors.initials: PM
authors.lastname: Bennett
authors.forename: T R
authors.initials: TR
authors.lastname: Walsh
authors.forename: A P
authors.initials: AP
authors.lastname: MacGowan
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D015169:Colony Count, Microbial / Q000379:methods; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin