title: AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.
abstract: The aim of thisin vivostudy was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistantStaphylococcus aureus(MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P= 0.343), while the medians (interquartile ranges [IQRs]) for log10CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P= 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.
authors.affiliation: Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia.
authors.forename: Ximena
authors.initials: X
authors.lastname: Castañeda
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: García-de-la-Mària
authors.affiliation: Hospital Parc Tauli de Sabadell, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Gasch
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pericas
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Armero
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-González
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Falces
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Ninot
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.|Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Almela
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Quintana
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vidal
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Fuster
authors.affiliation: Department of Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Llopis
authors.affiliation: Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Soto
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.|Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Marco
authors.affiliation: Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain jmmiro@ub.edu.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miró
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017850:Economics, Pharmaceutical; D004696:Endocarditis / Q000188:drug therapy*; D004697:Endocarditis, Bacterial / Q000188:drug therapy; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: MRSA; Staphylococcus aureus; experimental endocarditis; pharmacodynamic target; vancomycin MIC