Elution Characteristics of Antibiotics in Vancomycin Impregnated Bone Cement

  • Tae Young Kwon Department of Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University- Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
  • Kwang Bok Lee Department of Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University- Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea

Abstract

Treatment of osteomyelitis and prosthesis infections in the orthopedic area presents a difficult problem. Currently, Antibiotics impregnated bone cement made of Polymethyl methacrylate (PMMA) and calcium phosphate cement (CPC) has been used as a local treatmentof osteomyelitis. The characteristics of the dissolution of the antibiotic between CPC and PMMA has not been investigated. The purpose of this study is to compare the antibiotics release patterns of different cement types. We compared VCM concentrations in eluates from CPC (Novoset®; CBBio, Seoul, Korea) to those in eluates from 2 PMMA (Biomet Palacos®; Biomet Orthopaedics, Kerzer, Switzerland and Depuy CMW3®; DePuy International Ltd., England). The eluates were obtained on days 1, 2, 3, 7, and weeks 2, 3 and 4. HPLC (high-performance liquid chromatography) was applied to calculate the concentrations of VCM in thawed eluates of 3 groups, according to a Korean Pharmacopoeia vancomycin hydrochloride dissolution test method. The concentration of VCM eluted in CPC/VCM was maximum on day 1(595.81 μg VCM/ml), after which it showed a decreasing trend, but it continued to elute until the last observation. Compared with PMMA products, CPC/VCM released a large amount of antibiotics from day 1 to day 7, especially from day 1 to day 3, showing more than 15 times the amount of release. In addition, only a small amount of antibiotics was released in all samples after 2 weeks. CPC (Novoset) showed that the elution amount of antibiotics (VCM) was superior when compared to PMMA products. In addition, the dissolution persistence showed similar tendency between CPC and other PMMA cement products.

References

Nishitani, K., Beck, C.A., Rosenberg, A.F., Kates, S.L., Schwarz, E.M., Daiss, J.L., 2015. A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis. Clin Orthop Relat Res. 473(9):2735-49.

Moriarty, T.F., Kuehl, R., Coenye, T., Metsemakers, W.J., Morgenstern, M., Schwarz, E.M., Riool, M., Zaat, S.A.J., Khana, N., Kates, S.L., Richards, R.G., 2017. Orthopaedic device-related infection: current and future interventions for improved prevention and treatment. EFORT Open Rev. 1(4):89-99.

Inzana, J.A., Schwarz, E.M., Kates, S.L., Awad, H.A., 2016. Biomaterials approaches to treating implant-associated osteomyelitis. Biomaterials. 81:58-71.

Bariteau, J.T., Waryasz, G.R., McDonnell, M., Fischer, S.A., Hayda, R.A., Born, C.T., 2014. Fungal osteomyelitis and septic arthritis. J Am Acad Orthop Surg. 22(6):390-401.

van Vugt, T.A., Geurts, J., Arts, J.J., 2016. Clinical Application of Antimicrobial Bone Graft Substitute in Osteomyelitis Treatment: A Systematic Review of Different Bone Graft Substitutes Available in Clinical Treatment of Osteomyelitis. Biomed Res Int. 2016:6984656

Lalidou, F., Kolios, G., Drosos, G.I., 2014. Bone infections and bone graft substitutes for local antibiotic therapy. Surg Technol Int. 24:353-62.

Schlickewei, C.W., Yarar, S., Rueger, J.M., 2014. Eluting antibiotic bone graft substitutes for the treatment of osteomyelitis in long bones. A review: evidence for their use?. Orthop Res Rev. 6: 71-79.

Joseph, T.N., Chen, A.L., Di Cesare, P.E., 2003 Use of antibiotic-impregnated cement in total joint arthroplasty. J Am Acad Orthop Surg. 11(1):38-47.

Cui, Q., Mihalko, W.M., Shields, J.S., Ries, M., Saleh, K.J., 2007. Antibiotic-impregnated cement spacers for the treatment of infection associated with total hip or knee arthroplasty. J Bone Joint Surg Am. 89(4):871-82.

Jacobs, C., Christensen, C.P., Berend, M.E., 2009. Static and mobile antibiotic-impregnated cement spacers for the management of prosthetic joint infection. J Am Acad Orthop Surg. 17(6):356-68.

van de Belt, H., Neut, D., Uges, D.R., Schenk, W., van Horn, J.R., van der Mei, H.C., Busscher HJ., 2000. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials. 21(19):1981-7

Renno, A.C., van de Watering, F.C., Nejadnik, M.R., Crovace, M.C., Zanotto, E.D., Wolke, J.G., Jansen, J.A., van den Beucken, J.J., 2013. Incorporation of bioactive glass in calcium phosphate cement: An evaluation. Acta Biomater. 9(3):5728-39.

Urabe, K., Naruse, K., Hattori, H., Hirano, M., Uchida, K., Onuma, K., Park, H.J., Itoman, M., 2009. In vitro comparison of elution characteristics of vancomycin from calcium phosphate cement and polymethylmethacrylate. J Orthop Sci. 14(6):784-93.

Rybak, M.J., Lomaestro, B.M., Rotschafer, J.C., Moellering, R.C., Craig, W.A., Billeter, M., Dalovisio, J.R., Levine, D.P., 2009. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis. 49(3):325-7

van Hal, S.J., Paterson, D.L., 2011. Systematic review and meta-analysis of the significance of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates. Antimicrob Agents Chemother. 55(1):405-10.

Campbell, M.L., Marchaim, D., Pogue, J.M., Sunkara, B., Bheemreddy, S., Bathina, P., Pulluru, H., Chugh, N., Wilson, M.N., Moshos, J., Ku, K., Hayakawa, K., Martin, E.T., Lephart, P.R., Rybak, M.J., Kaye, K.S., 2012. Treatment of methicillin-resistant Staphylococcus aureus infections with a minimal inhibitory concentration of 2 μg/mL to vancomycin: old (trimethoprim/sulfamethoxazole) versus new (daptomycin or linezolid) agents. Ann Pharmacother. 46(12):1587-97.

Kalteis, T., Lüring, C., Gugler, G., Zysk, S., Caro, W., Handel, M., Grifka, J., 2004. Acute tissue toxicity of PMMA bone cements. Z Orthop Ihre Grenzgeb. 142(6):666-72. German.

Gibon, E., Córdova, L.A., Lu, L., Lin, T.H., Yao, Z., Hamadouche, M., Goodman, S.B., 2017. The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction. J Biomed Mater Res B Appl Biomater. 105(6):1685-1691.

Lodoso-Torrecilla, I., van den Beucken, J.J.J.P., Jansen, J.A., 2021. Calcium phosphate cements: Optimization toward biodegradability. Acta Biomater. 119:1-12.

Dorozhkin, S.V., 2009. Calcium orthophosphate cements and concretes. Materials. 2(1):221-91.

Low, K.L., Tan, S.H., Zein, S.H., Roether, J.A., Mouriño, V., Boccaccini, A.R., 2010. Calcium phosphate-based composites as injectable bone substitute materials. J Biomed Mater Res B Appl Biomater. 94(1):273-86.

Chen2, G., Liu, B., Liu, H., Zhang, H., Yang, K., Wang, Q., Ding, J., Chang, F., 2018. Calcium Phosphate Cement loaded with 10% vancomycin delivering high early and late local antibiotic concentration in vitro. Orthop Traumatol Surg Res. 104(8):1271-1275.

Published
2021-06-24
Section
Medicine