PMID- 28087408 OWN - NLM STAT- MEDLINE DCOM- 20171227 LR - 20220331 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 248 DP - 2017 Feb 28 TI - Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads. PG - 24-32 LID - S0168-3659(17)30002-0 [pii] LID - 10.1016/j.jconrel.2017.01.005 [doi] AB - 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 (CaSO(4)) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO(4) beads 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 CaSO(4) beads 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, CaSO(4) had 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. CI - Copyright (c) 2017 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Dusane, Devendra H AU - Dusane DH AD - Department of Microbial Infection and Immunity, The Ohio State University, Columbus 43210, USA. Electronic address: Devendra.Dusane@osumc.edu. FAU - Diamond, Scott M AU - Diamond SM AD - Department of Medicine, The Ohio State University, Columbus 43210, USA. FAU - Knecht, Cory S AU - Knecht CS AD - Department of Medicine, The Ohio State University, Columbus 43210, USA. FAU - Farrar, Nicholas R AU - Farrar NR AD - Department of Biomedical Engineering, The Ohio State University, Columbus 43210, USA. FAU - Peters, Casey W AU - Peters CW AD - Department of Biochemistry, The Ohio State University, Columbus 43210, USA. FAU - Howlin, Robert P AU - Howlin RP AD - Centre for Biological Sciences, Faculty of Natural & Environmental Sciences & Institute for Life Sciences, University of Southampton, Southampton, UK. FAU - Swearingen, Matthew C AU - Swearingen MC AD - Department of Microbial Infection and Immunity, The Ohio State University, Columbus 43210, USA. FAU - Calhoun, Jason H AU - Calhoun JH AD - Department of Muscoskeletal Sciences, Spectrum Health Medical Group, Grand Rapids, USA. FAU - Plaut, Roger D AU - Plaut RD AD - Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring 20993, USA. FAU - Nocera, Tanya M AU - Nocera TM AD - Department of Biomedical Engineering, The Ohio State University, Columbus 43210, USA. FAU - Granger, Jeffrey F AU - Granger JF AD - Department of Orthopaedics, The Ohio State University, Columbus 43210, USA. FAU - Stoodley, Paul AU - Stoodley P AD - 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. LA - eng PT - Journal Article DEP - 20170110 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Anti-Bacterial Agents) RN - 0 (Bone Cements) RN - 0 (Drug Carriers) RN - 6Q205EH1VU (Vancomycin) RN - 9011-14-7 (Polymethyl Methacrylate) RN - VZ8RRZ51VK (Tobramycin) RN - WAT0DDB505 (Calcium Sulfate) SB - IM MH - Anti-Bacterial Agents/*administration & dosage/pharmacology MH - Biofilms/*drug effects MH - Bone Cements/*chemistry MH - Calcium Sulfate/chemistry MH - Drug Carriers/*chemistry MH - Humans MH - Polymethyl Methacrylate/chemistry MH - Pseudomonas Infections/drug therapy MH - Pseudomonas aeruginosa/drug effects MH - Staphylococcal Infections/drug therapy MH - Staphylococcus aureus/drug effects MH - Tobramycin/*administration & dosage/pharmacology MH - Vancomycin/*administration & dosage/pharmacology OTO - NOTNLM OT - Antibiotic release OT - Biofilm OT - Bone cement OT - Periprosthetic infection OT - Zone of inhibition EDAT- 2017/01/15 06:00 MHDA- 2017/12/28 06:00 CRDT- 2017/01/15 06:00 PHST- 2016/06/06 00:00 [received] PHST- 2016/10/21 00:00 [revised] PHST- 2017/01/04 00:00 [accepted] PHST- 2017/01/15 06:00 [pubmed] PHST- 2017/12/28 06:00 [medline] PHST- 2017/01/15 06:00 [entrez] AID - S0168-3659(17)30002-0 [pii] AID - 10.1016/j.jconrel.2017.01.005 [doi] PST - ppublish SO - J Control Release. 2017 Feb 28;248:24-32. doi: 10.1016/j.jconrel.2017.01.005. Epub 2017 Jan 10.