title: Penetration of daptomycin into bone and synovial fluid in joint replacement.
abstract: Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.
authors.affiliation: Laboratoire de Pharmacologie Clinique et Toxicologie, Centre Hospitalier Universitaire de Besançon, Besançon, France EA 3920, Marqueurs Pronostiques et Facteurs de Régulations des Pathologies Cardiaques et Vasculaires-SFR FED 4234, Université de Franche Comté, Besançon, France.
authors.forename: D
authors.initials: D
authors.lastname: Montange
authors.affiliation: Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire de Besançon, Besançon, France.
authors.forename: F
authors.initials: F
authors.lastname: Berthier
authors.affiliation: Service d'Orthopédie, de Traumatologie, de Chirurgie Plastique, Reconstructrice et Assistance Main, Centre Hospitalier Universitaire de Besançon, Besançon, France EA 4268, Innovation, Imagerie, Ingénierie et Intervention de Santé I4S-SFR FED 4234 INSERM, Université de Franche Comté, Besançon, France.
authors.forename: G
authors.initials: G
authors.lastname: Leclerc
authors.affiliation: Service d'Orthopédie, de Traumatologie, de Chirurgie Plastique, Reconstructrice et Assistance Main, Centre Hospitalier Universitaire de Besançon, Besançon, France.
authors.forename: A
authors.initials: A
authors.lastname: Serre
authors.affiliation: Service d'Orthopédie, de Traumatologie, de Chirurgie Plastique, Reconstructrice et Assistance Main, Centre Hospitalier Universitaire de Besançon, Besançon, France.
authors.forename: L
authors.initials: L
authors.lastname: Jeunet
authors.affiliation: Laboratoire de Pharmacologie Clinique et Toxicologie, Centre Hospitalier Universitaire de Besançon, Besançon, France.
authors.forename: M
authors.initials: M
authors.lastname: Berard
authors.affiliation: Laboratoire de Pharmacologie Clinique et Toxicologie, Centre Hospitalier Universitaire de Besançon, Besançon, France UMR 1098, Université de Franche-Comté, Besançon, France.
authors.forename: P
authors.initials: P
authors.lastname: Muret
authors.affiliation: DRCI, Centre Hospitalier Universitaire de Besançon, Besançon, France.
authors.forename: L
authors.initials: L
authors.lastname: Vettoretti
authors.affiliation: Service des Maladies Infectieuses, Centre Hospitalier Universitaire de Besançon, Besançon, France.
authors.forename: J
authors.initials: J
authors.lastname: Leroy
authors.affiliation: Service des Maladies Infectieuses, Centre Hospitalier Universitaire de Besançon, Besançon, France UMR CNRS Chrono-environnement, Université de Franche-Comté, Besançon, France.
authors.forename: B
authors.initials: B
authors.lastname: Hoen
authors.affiliation: Service des Maladies Infectieuses, Centre Hospitalier Universitaire de Besançon, Besançon, France UMR CNRS Chrono-environnement, Université de Franche-Comté, Besançon, France cchirouze@chu-besancon.fr.
authors.forename: C
authors.initials: C
authors.lastname: Chirouze
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D019643:Arthroplasty, Replacement; D001842:Bone and Bones / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D017576:Daptomycin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin