title: Antibiotic-loaded synthetic calcium sulfate beads for prevention of bacterial colonization and biofilm formation in periprosthetic infections.
abstract: Periprosthetic infection (PI) causes significant morbidity and mortality after fixation and joint arthroplasty and has been extensively linked to the formation of bacterial biofilms. Poly(methyl methacrylate) (PMMA), as a cement or as beads, is commonly used for antibiotic release to the site of infection but displays variable elution kinetics and also represents a potential nidus for infection, therefore requiring surgical removal once antibiotics have eluted. Absorbable cements have shown improved elution of a wider range of antibiotics and, crucially, complete biodegradation, but limited data exist as to their antimicrobial and antibiofilm efficacy. Synthetic calcium sulfate beads loaded with tobramycin, vancomycin, or vancomycin-tobramycin dual treatment (in a 1:0.24 [wt/wt] ratio) were assessed for their abilities to eradicate planktonic methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis relative to that of PMMA beads. The ability of the calcium sulfate beads to prevent biofilm formation over multiple days and to eradicate preformed biofilms was studied using a combination of viable cell counts, confocal microscopy, and scanning electron microscopy of the bead surface. Biofilm bacteria displayed a greater tolerance to the antibiotics than their planktonic counterparts. Antibiotic-loaded beads were able to kill planktonic cultures of 10(6) CFU/ml, prevent bacterial colonization, and significantly reduce biofilm formation over multiple days. However, established biofilms were harder to eradicate. These data further demonstrate the difficulty in clearing established biofilms; therefore, early preventive measures are key to reducing the risk of PI. Synthetic calcium sulfate loaded with antibiotics has the potential to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material and, thus, to reduce the rates of periprosthetic infection.
authors.affiliation: National Institute for Health Research Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom Centre for Biological Sciences, Faculty of Natural and Environmental Sciences and Institute for Life Sciences, University of Southampton, Highfield, Southampton, United Kingdom.
authors.forename: R P
authors.initials: RP
authors.lastname: Howlin
authors.affiliation: Biocomposites Ltd., Keele Science Park, Keele, Staffordshire, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Brayford
authors.affiliation: National Institute for Health Research Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom Centre for Biological Sciences, Faculty of Natural and Environmental Sciences and Institute for Life Sciences, University of Southampton, Highfield, Southampton, United Kingdom.
authors.forename: J S
authors.initials: JS
authors.lastname: Webb
authors.affiliation: Biocomposites Ltd., Keele Science Park, Keele, Staffordshire, United Kingdom.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cooper
authors.affiliation: Biocomposites Ltd., Keele Science Park, Keele, Staffordshire, United Kingdom.
authors.forename: S S
authors.initials: SS
authors.lastname: Aiken
authors.affiliation: National Institute for Health Research Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom National Centre for Advanced Tribology, Faculty of Engineering and Institute for Life Sciences, University of Southampton, Highfield, Southampton, United Kingdom Departments of Microbial Infection and Immunity and Orthopedics, Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, USA pstoodley@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Stoodley
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D001843:Bone Cements / Q000009:adverse effects; D002133:Calcium Sulfate / Q000494:pharmacology*; D004338:Drug Combinations; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D016459:Prosthesis-Related Infections / Q000188:drug therapy / Q000517:prevention & control*; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D014031:Tobramycin / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D004338:Drug Combinations; D014640:Vancomycin; D014031:Tobramycin; D002133:Calcium Sulfate