title: Size and composition of synthetic calcium sulfate beads influence dissolution and elution rates in vitro.
abstract: Treatments of osteomyelitis lag behind bacterial resistance to antibiotics. We tested different-sized calcium sulfate beads and their ability to elute multiple antibiotics in vitro as a possible method to improve the therapeutic delivery in patients. Two sizes of calcium sulfate beads (4.8 and 3.0 mm diameter) that contained vancomycin, tobramycin, or both were dissolved in phosphate-buffered saline, and the rate of dissolution by weight and antibiotic elution by the disc diffusion assay and high-pressure liquid chromatography were measured. The 4.8 mm beads showed significantly higher dissolution rates relative to the 3.0 mm beads (2.3 mg/day vs. 1.3 mg/day). While the vancomycin-loaded 4.8 mm beads eluted for a longer time relative to the 3.0 mm beads (20 days vs. 10 days), the smaller beads had threefold higher elution for the first 2 days, before dropping to near zero elution by day 4. The presence of tobramycin extended the elution of the vancomycin to day 40, which closely matches the recommended 6 weeks to treat orthopedic staphylococcus infections. These data suggest that size and content of the bead are variables that could affect their clinical success, and both could be exploited to tailor treatments of specific infections and injuries.
authors.affiliation: Department of Orthopaedics, The Ohio State University Wexner Medical Center, Columbus, Ohio, 43210.
authors.forename: Randy
authors.initials: R
authors.lastname: Roberts
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McConoughey
authors.forename: Jason H
authors.initials: JH
authors.lastname: Calhoun
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002133:Calcium Sulfate / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D052978:Disk Diffusion Antimicrobial Tests; D004337:Drug Carriers; D004339:Drug Compounding; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D014031:Tobramycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D014640:Vancomycin; D014031:Tobramycin; D002133:Calcium Sulfate
keywords: antibiotics; calcium sulfate; elution