OTA 2005 Posters

Scientific Poster #49 Basic Science

:The In Vitro Elution Characteristics of Antifungal-loaded Polymethylmethacrylate (PMMA) and Calcium Sulfate Bone Cements

Christopher Grimsrud, MD, PhD¹ (n); Raymond Raven, MD¹ (n);

A.W. Fothergill, MA, MBA (n)²; Hubert Kim, MD, PhD¹ (a-Pfizer);

¹Department of Orthopaedic Surgery, University of California,

San Francisco, California, USA

²Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Purpose: This study was conducted to determine the quantity and bioactivity of antifungal agents eluted from bone cement beads. In a few case reports, PMMA loaded with amphotericin has been used successfully in the treatment of deep fungal infections. Newer antifungal drugs, such as the "second generation" triazole Voriconzole, are less toxic and have superior efficacy against a broad spectrum of fungi and yeast. However, there are no data on the elution properties of these newer antifungals from bone cements. We proposed to define the in vitro elution characteristics and bioactivity of Voriconazole released from PMMA and calcium sulfate cements.

Methods: Antifungal-loaded Palacos (Biomet) PMMA and Osteoset (Wright Medical) calcium sulfate cement beads were prepared by combining the antibiotic with the cements in a 1:10 ratio by weight. Each bead measured 1 cm in diameter. The beads were immersed in a 2.5-ml bath of phosphate-buffered normal saline at room temperature and placed on a shaker. Samples were obtained at 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 1 week, and 2 weeks. The concentration of antifungal in each sample was determined using high pressure liquid chromatography (HPLC). The bioactivity of the each sample was determined using macrobroth dilution and plate diffusion methods.

Results: PMMA beads eluted extremely high levels of Voriconazole (>100 µg/ml/24 hours) for the first 2 days. By day 14, levels had decreased severalfold (33 µg/ml/24 hours). Calcium sulfate beads eluted extremely high levels of Voriconazole (>100 µg/ml/24 hours) for the full 14 days. In all cases, antifungal levels were maintained throughout the 14-day
experiment, and bioactivity correlated with the amount of Voriconazole measured by HPLC.

Conclusion/Significance: PMMA and calcium sulfate are effective carriers of the antifungal drug Voriconazole. The Voriconazole continues to elute out of the PMMA and calcium sulfate beads over a period of at least 2 weeks. The drug remains biologically active even with the heat generated during PMMA polymerization. Higher levels of Voriconazole elute over time from calcium sulfate beads than from PMMA beads. PMMA and calcium sulfate can deliver fungicidal concentrations of Voriconazole in vitro. Potentially, this finding may prove useful for the management of orthopaedic fungal infections that are notoriously difficult to treat.