JBiSE  Vol.7 No.6 , May 2014
Modeling of Daptomycin Release from Medium-Dose Daptomycin-Xylitol-Loaded PMMA Bone Cements
Antibiotic-loaded poly (methyl methacrylate) bone cements (ALPBCs) are widely used as an agent to decrease the occurrence of periprosthetic joint infection (PJI). Most often, the antibiotic used in an ALPBC is gentamicin, tobramycin, or vancomycin. In many recent clinical studies, it has been reported that the pathogens that commonly present in PIJ are becoming resistant to these antibiotics. As such, a new generation of antibiotics is emerging, among which is daptomycin. Literature reports with a clinically relevant medium-dose daptomycin-loaded cement show that the daptomycin release rate from cylindrical specimens is low. Incorporation of a poragen, such as dextrose, glycine, or particulate xylitol, into the cement powder has been shown to be an effective way to increase daptomycin release rate. There are, however, no studies on modeling of daptomycin release from specimens of either a daptomycin-loaded cement or a daptomycin-poragen-loaded cement. In the present work, we determine the profiles of daptomycin release from cylindrical medium-dose daptomycin-xylitol-loaded cement specimens, as a function of the particulate xylitol loading. We used these results and relationships that have been shown to model antibiotic release from ALPBC specimens to obtain the best-fit relationship for the present cements. Through this approach, we demonstrated that, regardless of the xylitol loading, the daptomycin release profile is a mixture of initial burst followed by a slow Fickian diffusion.

Cite this paper
Salehi, A. , Lewis, G. , Parker, A. and Haggard, W. (2014) Modeling of Daptomycin Release from Medium-Dose Daptomycin-Xylitol-Loaded PMMA Bone Cements. Journal of Biomedical Science and Engineering, 7, 351-360. doi: 10.4236/jbise.2014.76037.
[1]   Hirakawa, K., Stulberg, B.N., Wilde, A.H., Bauer, T.W. and Secic, M. (1998) Results of 2-Stage Reimplantation for Infected Total Knee Arthroplasty. The Journal of Arthroplasty, 13, 22-28.

[2]   Trampuz, A. and Zimmerlt, W. (2005) Prosthetic Joint Infections: Update in Diagnosis and Treatment. Swiss Medical Weekly, 135, 243-251.

[3]   Lentino, J.R. (2003) Prosthetic Joint Infections: Bane of Orthopedists, Challenge for Infectious Disease Specialists. Clinical Infectious Diseases, 36, 1157-1161.

[4]   Parvizi, J., Adeli, B., Zmistowski, B., Restrepo, C. and Greenwald, A.S. (2012) Management of Periprosthetic Joint Infection: The Current Knowledge. The Journal of Bone & Joint Surgery, 94, e104(1-9).

[5]   Parvizi, J., Pawasarat, I.M., Azzam, K.A., Joshi, A., Hansen, E.N. and Bozic, K.J. (2010) Periprosthetic Joint Infection: The Economic Impact of Methicillin-Resistant Infections. The Journal of Arthroplasty, 25, 103-107.

[6]   Kurtz, S.M., Lau, E., Watson, H., Schmer, J.K. and Parvizi, J. (2012) Economic Burden of Periprosthetic Joint Infection in the United States. The Journal of Arthroplasty, 27, 61-65e1.

[7]   Jiranek, W.A., Hanssen, A.D. and Greenwald, A.S. (2006) Antibiotic-Loaded Bone Cement for Infection Prophylaxis in Total Joint Replacement. The Journal of Bone & Joint Surgery, 88, 2487-2500.

[8]   Parvizi, J., Saleh, K.J., Ragland, P.S., Pour, A.E. and Mont, M.A. (2008) Efficacy of Antibiotic-Impregnated Cement in Total Hip Replacement: A Meta-Analysis. Acta Or-thopaedica, 79, 335-3341.

[9]   Meyer, J., Piller, G., Spiegel, C.A., Hetzel, S. and Squire, M. (2011) Vacuum-Mixing Significantly Changes Antibiotic Elution Characteristics of Commercially Available Antibiotic-Impregnated Bone Cements. The Journal of Bone & Joint Surgery, 93, 2049-2056.

[10]   Wenzel, R.P. (2004) The Antibiotic Pipeline—Challenges, Costs, and Values. The New England Journal of Medicine, 351, 523-526.

[11]   Campoccia, D., Montanaro, L. and Arciola, C.R. (2006) The Significance of Infection Related to Orthopedic Devices and Issues of Antibiotic Resistance. Biomaterial, 27, 2331-2339.

[12]   Higgins, D.L., Chang, R., Debabov, D.V., Leung, J., Wu, T., Krause, K.M., Sandvik, E., Hubbard, J.M., Kaniga, K., Schmidt Jr., D.E., Gao, Q., Cass, R.T., Karr, D.E., Benton, B.M. and Humphrey, P.P. (2005) Telavancin, a Multifunctional Lipoglycopeptide, Disrupts Both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant Staphylococcus aureus. Antimicrob Agent Chemotherapy, 49, 1127-1134.

[13]   Doan, T.L., Fung, H.B., Mehta, D. and Riska, P.F. (2006) Tigecycline: A Glycocycline Antimicrobial Agent. Clinical Therapy, 28, 1079-1086.

[14]   Sauermann, R., Rothenburger, M., Graninger, W. and Joukhadar, C. (2008) Daptomycin: A Review 4 Years after First Approval. Pharmacology, 81, 79-91.

[15]   Song, J.-H. (2008) What’s New on the Antimicrobial Horizon? International Journal of Antimicrobial Agents, 32, S207-S213.

[16]   Huang, V., Cheung, C.M., Kaatz, G.W. and Rybak, M.J. (2010) Evaluation of Dalbavancin, Tigecycline, Minocycline, Tetracycline, Teicoplanin and Vancomycin against Community-Associated and Multidrug-Resistant Hospital-Associated Methicillin-Resistant Staphylococcus aureus. International Journal of Antimicrobial Agents, 35, 25-29.

[17]   Cai, Y., Wang, R., Liang, B., Bai, N. and Liu, Y. (2011) Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease. Antimicrobial Agents and Chemotherapy, 55, 1162-1172.

[18]   Licitra, C.M., Crespo, A., Licitra, D. and Wallis-Crespo, M.C. (2011) Daptomycin for the Treatment of Osteomyelitis and Prosthetic Joint Infection: Retrospective Analysis of Efficacy and Safety in an Outpatient Infusion Center. The Internet Journal of Infectious Diseases, 9, Published Online.

[19]   Kaushal, R. and Hassoun, A. (2012) Successful Treatment of Methicillin-Resistant Staphylococcus epidermidis Prosthetic Joint Infection with Telavancin. Journal of Antimicrobial Chemo-therapy, 67, 2052-2053.

[20]   Rouse, M.S., Piper, K.E., Jacobson, M., Jacofsky, D.J., Steckelberg, J.M. and Patel, R. (2006) Daptomycin Treatment of Staphylococcus aureus Experimental Chronic Osteomyelitis. Journal of Antimicrobial Chemotherapy, 57, 301-305.

[21]   Lewis, G., Brooks, J.L., Courtney, H.S., Li, Y. and Haggard, W.O. (2010) An Approach for Determining Antibiotic Loading for a Physician-Directed Antibiotic-Loaded PMMA Bone Cement Formulation. Clinical Orthopaedics and Related Research, 468, 2092-2100.

[22]   Chang, Y., Chen, W.C., Hsieh, P.H., Chen, D.W., Lee, M.S., Shih, H.N. and Ueng, S.W.N. (2011) In Vitro Activities of Daptomycin-, Vancomycin-, and Teicoplanin-Loaded Polymethylmethacrylate against Methicillin-Susceptible, Methicillin-Resistant, and Vancomycin-Intermediate Strains of Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 55, 5480-5484.

[23]   Kaplan, L., Kurdzeil, M., Baker, K.C. and Verner, J. (2012) Characterization of Daptomycin-Loaded Antibiotic Cement. Orthopedics, 35, e503-e509.

[24]   McLaren, A.C., McLaren, S.G. and Smeltzer, M. (2006) Xylitol and Glycine Fillers Increase Permeability of PMMA to Enhance Elution of Daptomycin. Clinical Orthopaedics and Related Research, 451, 25-28.

[25]   Salehi, A., Parker, A.C., Lewis, G., Courtney, H.S. and Haggard, W.O. (2013) A Daptomycin-Xylitol-Loaded Polyme-thylmethacrylate Bone Cement: How Much Xylitol Should Be Used? Clinical Orthopaedics and Related Research, 471, 3149-3157.

[26]   Frutos, G., Pastor, J.Y., Martínez, N., Virto, M.R. and Torrado, S. (2010) Influence of Lactose Addition to Gentamicin-Loaded Acrylic Bone Cement on the Kinetics of Release of the Antibiotic and the Cement Properties. Acta Biomaterialia, 6, 804-811.

[27]   Nugent, M., McLaren, A., Vernon, B. and McLemore, R. (2010) Strength of Antimicrobial Bone Cement Decreases with Increased Poragen Fraction. Clinical Orthopaedics and Related Research, 468, 2101-2106.

[28]   Liu, W.C., Wong, C.T., Fong, M.K., Cheung, W.S., Kao, R.Y.I., Luk, K.D.K. and Lu, W.W. (2010) Gentamicin-Loaded Strontium-Containing Hydroxyapatite Bioactive Bone Cement--An Efficient Bioactive Antibiotic Drug Delivery System. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 95B, 397-406.

[29]   Shen, S.C, Ng, W.K., Shi, Z., Chia, L., Neoh, K.G. and Tan, R.B.H. (2011) Mesoporous Silica Nanoparticle-Functionalized Poly (Methyl Methacrylate)-Based Bone Cement for Effective Antibiotics Delivery. Journal of Materials Science: Materials in Medicine, 22, 2283-2292.

[30]   Masri, B.A., Duncan, C.P., Beauchamp, C.P., Paris, N.J. and Arntorp, J. (1995) Effect of Varying Surface Patterns on Antibiotic Elution from Antibiotic-loaded Bone Cement. The Journal of Arthroplasty, 10, 453-459.

[31]   Cai, X.Z., Chen, X.Z., Yan, S.G., Ruan, Z.R., Yan, R.J., Ji, K. and Xu, J. (2009) Intermittent Watt-Level Ultrasonication Facilitates Vancomycin Release from Therapeutic Acrylic Bone Cement. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 90B, 11-17.

[32]   Shiramizu, K., Lovric, V., Leung, A. and Walsh, W.R. (2008) How Do Porosity-Inducing Techniques Affect Antibiotic Elution from Bone Cement? An Intro Comparison between Hydrogen Peroxide and a Mechanical Mixer. Journal of Orthopaedics and Traumatology, 9, 17-22.

[33]   Beenken, K.E., Bradney, L., Bellamy, W., Skinner, R.A., McLaren, S.G., Gruenwald, M.J., Spencer, H.J., Smith, J.K., Haggard, W.O. and Smeltzer, M.S. (2012) Use of Xylitol to Enhance the Therapeutic Efficacy of Polymethylmethacry-late-Based Antibiotic Therapy in Treatment of Chronic Osteomyelitis. Antimicrobial Agents and Chemotherapy, 56, 5839-5844.

[34]   Klekamp, J., Dawson, J.M., Haas, D.W., DeBoer, D. and Christie, M. (1999) The Use of Vancomycin and Tobramycin in Acrylic Bone Cement: Biomechanical Effects and Elution Kinetics for Use in Joint Arthroplasty. The Journal of Arthroplasty, 14, 339-346.

[35]   Frutos, P., Diez-Peña, E., Frutos, G. and Barrales-Rienda, J.M. (2002) Release of Gentamicin Sulphate from a Modified Commercial Bone Cement. Effect of (2-Hydroxyethyl Methacrylate) Comonomer and Poly (N-vinyl-2-pyrrolidone) Additive on Release Mechanism and Kinetics. Biomaterials, 23, 3787-3797.

[36]   American Society for Testing and Materials (ASTM) (2011) Standard F 2118-10 (Approved December 1, 2010): Standard Test Method for Constant Amplitude of Force Controlled Fatigue Testing of Acrylic Bone Cement Materials. ASTM International, West Conshohocken.

[37]   Richelsoph, K.C., Webb, N.D. and Haggard, W.O. (2007) Elution Behavior of Daptomycin-Loaded Calcium Sulfate Pellets: A Preliminary Study. Clinical Orthopaedics & Related Research, 461, 68-73.

[38]   Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P. and Peppas, N.A. (1983) Mechanisms of Solute Release from Porous Hydrophilic Polymers. International Journal of Pharmaceutics, 15, 25-35.

[39]   Lindner, W.D. and Lippold, B.C. (1995) Drug Release from Hydrocolloid Embedding with High or Low Susceptibility to Hydrodynamic Stress. Pharmaceutical Research, 12, 1781-1785.

[40]   Hesaraki, S., Moztarzadeh, F., Nemati, R. and Nezafati, N. (2009) Preparation and Characterization of Calcium Sulfate-Biomimetic Apatite Nanocomposites for Controlled Release of Antibiotics. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 91B, 651-661.

[41]   Noyes, A.A. and Whitney, W.R. (1897) The Rate of Solution of Solid Substances in Their Own Solutions. Journal of the American Chemical Society, 19, 930-934.

[42]   Anagnostakos, K. and Kelm, J. (2009) Enhancement of Antibiotic Elution from Acrylic Bone Cement. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 90B, 467-475.

[43]   Lewis, G. (2009) Properties of Antibiotic-Loaded Acrylic Bone Cements for Use in Cemented Arthroplasties: A State-of-the-Art Review. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 89B, 558-574.

[44]   Siepmann, J. and Peppas, N.A. (2001) Modeling of Drug Release from Delivery Systems Based on Hydroxypropyl Methylcellulose (HPMC). Advanced Drug Delivery Reviews, 48, 139-157.

[45]   Kühn, K.D. (2000) Bone Cements: Up-to-Date Comparison of Physical and Chemical Properties of Commercial Materials. Springer-Verlag, Berlin.

[46]   Mattila, P.T., Svanberf, M.J., Jämsä, T. and Knuuttila, M.L.E. (2002) Improved Bone Biomechanical Properties in Xylitol-Fed Aged Rats. Metabolism, Clinical and Experimental, 51, 92-96.

[47]   Gálvez-Lopez, R., Peña-Monje, A., Antelo-Lorenzo, R., Guardia-Olmedo, J., Moliz, J., Hernández-Quero, J. and Parra-Ruiz, J. (2014) Elution Kinetics, Antimicrobial Activity, and Mechanical Properties of 11 Different Antibiotic Loaded Acrylic Bone Cement. Diagnostic Microbiology & Infectious Disease, 78, 70-74.