title: The in vitro elution characteristics of antifungal-loaded PMMA bone cement and calcium sulfate bone substitute.
abstract: The use of antimicrobial-loaded delivery vehicles, most often as antibiotic beads, is common practice for the treatment of deep musculoskeletal infections. The elution of antibacterial drugs from various bone cements has been extensively studied. However, much less is known about the elution of other antimicrobials from these materials. In particular, the use of this approach for fungal infections has not been well studied despite growing concern about these difficult-to-treat organisms. Voriconazole is a broad-spectrum and highly effective antifungal that has been used in the treatment of resistant fungal pathogens. We examined the in vitro elution characteristics of voriconazole from nonabsorbable polymethylmethacrylate (PMMA) beads and from absorbable calcium sulfate beads. Voricanazole-containing beads were immersed in a 5-mL bath of phosphate-buffered saline at room temperature and placed on an orbital shaker. Eluent samples were collected over the course of 2 weeks. Concentrations of the antifungal drug in solution were measured using high-performance liquid chromatography. To verify biologic activity of the eluted antifungal, collected samples were also tested against control yeasts. We found that samples collected out to 2 weeks contained relatively high voriconazole concentrations and enough active antifungal activity to inhibit growth of the control yeasts. These data demonstrate that voriconazole retains its antifungal activity when mixed into either PMMA or calcium sulfate beads, and elutes out of beads at biologically effective concentrations over a time period of at least 2 weeks. Therefore, incorporation of voriconazole into either absorbable or nonabsorbable beads appears to be a reasonable strategy for the local delivery of a potent, broad-spectrum antifungal agent to an infected wound bed.
authors.affiliation: Department of Orthopedic Surgery, University of California, San Francisco, California 94143, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grimsrud
authors.forename: Raymond
authors.initials: R
authors.lastname: Raven
authors.forename: A W
authors.initials: AW
authors.lastname: Fothergill
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
mesh_terms: D000935:Antifungal Agents / Q000032:analysis*; D001843:Bone Cements / Q000737:chemistry*; D018786:Bone Substitutes / Q000737:chemistry*; D002133:Calcium Sulfate / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D019904:Polymethyl Methacrylate / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013997:Time Factors; D014230:Triazoles / Q000737:chemistry*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D001843:Bone Cements; D018786:Bone Substitutes; D004337:Drug Carriers; D011743:Pyrimidines; D012997:Solvents; D014230:Triazoles; D019904:Polymethyl Methacrylate; D065819:Voriconazole; D002133:Calcium Sulfate