title: Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads.
abstract: Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria. Short-term release into an agar gel was evaluated using a fluorescent tracer (fluorescein) incorporated in the carrier materials calcium sulfate (CaSO4) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO4beads were evaluated. Mechanical properties of fluorescein-incorporated beads were analyzed. Efficacy of the antibiotics vancomycin (VAN) or tobramycin (TOB) alone and in combination was evaluated against lawn biofilms of bioluminescent strains of Staphylococcus aureus and Pseudomonas aeruginosa. Zones of inhibition of cultures (ZOI) were measured visually and using an in-vivo imaging system (IVIS). The influence of body fluids on release was assessed using CaSO4beads that contained fluorescein or antibiotics and were pre-coated with human blood or synovial fluid. The spread from the beads followed a square root of time relationship in all cases. The loading concentration had no influence on short-term fluorescein release and pre-coating of beads with body fluids did not affect short-term release or antibacterial activity. Compared to PMMA, CaSO4had a more rapid short term rate of elution and activity against planktonic and lawn biofilms. This study highlights the importance of considering antibiotic loading and packing density when investigating the clinical application of bone cements for infection management.
authors.affiliation: Department of Microbial Infection and Immunity, The Ohio State University, Columbus 43210, USA. Electronic address: Devendra.Dusane@osumc.edu.
authors.forename: Devendra H
authors.initials: DH
authors.lastname: Dusane
authors.affiliation: Department of Medicine, The Ohio State University, Columbus 43210, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Diamond
authors.affiliation: Department of Medicine, The Ohio State University, Columbus 43210, USA.
authors.forename: Cory S
authors.initials: CS
authors.lastname: Knecht
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus 43210, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Farrar
authors.affiliation: Department of Biochemistry, The Ohio State University, Columbus 43210, USA.
authors.forename: Casey W
authors.initials: CW
authors.lastname: Peters
authors.affiliation: Centre for Biological Sciences, Faculty of Natural & Environmental Sciences & Institute for Life Sciences, University of Southampton, Southampton, UK.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Howlin
authors.affiliation: Department of Microbial Infection and Immunity, The Ohio State University, Columbus 43210, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Swearingen
authors.affiliation: Department of Muscoskeletal Sciences, Spectrum Health Medical Group, Grand Rapids, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Calhoun
authors.affiliation: Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring 20993, USA.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Plaut
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus 43210, USA.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Nocera
authors.affiliation: Department of Orthopaedics, The Ohio State University, Columbus 43210, USA.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Granger
authors.affiliation: Department of Microbial Infection and Immunity, The Ohio State University, Columbus 43210, USA; Department of Orthopaedics, The Ohio State University, Columbus 43210, USA; National Center for Advanced Tribology at Southampton (nCATS), Engineering and the Environment, University of Southampton SO17 1BJ, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Stoodley
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D001843:Bone Cements / Q000737:chemistry*; D002133:Calcium Sulfate / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019904:Polymethyl Methacrylate / Q000737:chemistry; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D014031:Tobramycin / Q000008:administration & dosage* / Q000494:pharmacology; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D004337:Drug Carriers; D014640:Vancomycin; D019904:Polymethyl Methacrylate; D014031:Tobramycin; D002133:Calcium Sulfate
keywords: Antibiotic release; Biofilm; Bone cement; Periprosthetic infection; Zone of inhibition