Advertisement

Clinical Orthopaedics and Related Research®

, Volume 468, Issue 8, pp 2092–2100 | Cite as

An Approach for Determining Antibiotic Loading for a Physician-directed Antibiotic-loaded PMMA Bone Cement Formulation

  • Gladius Lewis
  • Jennifer L. BrooksEmail author
  • Harry S. Courtney
  • Yuan Li
  • Warren O. Haggard
Symposium: Papers Presented at the 2009 Meeting of the Musculoskeletal Infection Society

Abstract

Background

When a physician-directed antibiotic-loaded polymethylmethacrylate (PMMA) bone cement (ALBC) formulation is used in total hip arthroplasties (THAs) and total knee arthroplasties (TKAs), current practice in the United States involves arbitrary choice of the antibiotic loading (herein defined as the ratio of the mass of the antibiotic added to the mass of the cement powder). We suggest there is a need to develop a rational method for determining this loading.

Questions/purposes

We propose a new method for determining the antibiotic loading to use when preparing a physician-directed ALBC formulation and illustrate this method using three in vitro properties of an ALBC in which the antibiotic was daptomycin.

Materials and Methods

Daptomycin was blended with the powder of the cement using a mechanical mixer. We performed fatigue, elution, and activity tests on three sets of specimens having daptomycin loadings of 2.25, 4.50, and 11.00 wt/wt%. Correlational analyses of the results of these tests were used in conjunction with stated constraints and a nonlinear optimization method to determine the daptomycin loading to use.

Results

With an increase in daptomycin loading, the estimated mean fatigue limit of the cement decreased, the estimated elution rate of the antibiotic increased, and the percentage inhibition of staphylococcal growth by the eluate remained unchanged at 100%. For a daptomycin-loaded PMMA bone cement we computed the optimum amount of daptomycin to mechanically blend with 40 g of cement powder is 1.36 g.

Conclusions

We suggest an approach that may be used to determine the amount of antibiotic to blend with the powder of a PMMA bone cement when preparing a physician-directed ALBC formulation, and highlighted the attractions and limitations of this approach.

Clinical Relevance

When a physician-directed ALBC formulation is selected for use in a TKA or THA, the approach we detail may be employed to determine the antibiotic loading to use rather than the empirical approach that is taken in current clinical practice.

Keywords

PMMA Fatigue Life Tobramycin Bone Cement Fatigue Limit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Cubist Pharmaceuticals and Wright Medical Technology for generous donation of the daptomycin and the bone cement, respectively, used in this investigation and Dr. Teong Tan for help with the optimization work.

References

  1. 1.
    American Society for Testing and Materials (ASTM). Standard F 2118-03: Standard test method for constant amplitude of force controlled fatigue testing of acrylic bone cement materials. In: Annual Book of ASTM Standards 2008, Vol 13.01. West Conshohocken, PA: ASTM International; 2008:1136–1143.Google Scholar
  2. 2.
    Australian Orthopaedics Association. National Joint Replacement Registry. Annual Report. Adelaide, Australia: AOA; 2009:169–177.Google Scholar
  3. 3.
    Bates DM, Watts DG. Nonlinear Regression and Its Applications. New York, NY: Wiley; 1988.CrossRefGoogle Scholar
  4. 4.
    Burdette SD. Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine. Spine J. 2009;9:e5–e8.CrossRefPubMedGoogle Scholar
  5. 5.
    Davis JP, Harris WH. Effect of hand mixing tobramycin on fatigue strength of Simplex P. J Biomed Mater Res. 1991;25:1409–1414.CrossRefGoogle Scholar
  6. 6.
    Diefenbeck M, Muckley T, Hofmann GO. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury. 2006;37:S95–S104.CrossRefPubMedGoogle Scholar
  7. 7.
    Dunne N, Hill J, McAfee P, Todd K, Kirkpatrick R, Tunney M, Patrick S. In vitro study of the efficacy of acrylic bone cement loaded with supplementary amounts of gentamicin: effects on mechanical properties, antibiotic release, and biofilm formation. Acta Orthop. 2007;78:774–785.CrossRefPubMedGoogle Scholar
  8. 8.
    Falagas ME, Giannopoulou KP, Ntziora F, Papagelopoulos PJ. Daptomycin for treatment of patients with bone and joint infections: a systematic review of the clinical evidence. Int J Antimicrob Agents. 2007;30:202–209.CrossRefPubMedGoogle Scholar
  9. 9.
    He S, Scott C, Higham P. Mixing of acrylic bone cement: effect of oxygen on setting properties. Biomaterials. 2003;30:202–209.Google Scholar
  10. 10.
    Hendriks JGE, Neut D, Hazenberg JG, verkerke GJ, van Horn JR, van der Mei HC, Busscher HJ. The influence of cyclic loading on gentamicin release from acrylic bone cements. J Biomech. 2005;38:953–957.CrossRefPubMedGoogle Scholar
  11. 11.
    Jasty M, Moloney WJ, Bragdon CR, O’Connor D, Haire T, Harris WH. The initiation of failur e in cemented femoral components of hip arthroplasties. J Bone Joint Surg. 1991;73:551–558.Google Scholar
  12. 12.
    Jiranek WA, Hanssen AD, Greenwald AS. Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement. J Bone Joint Surg Am. 2006;88:2487–2500.CrossRefPubMedGoogle Scholar
  13. 13.
    Klekamp J, Dawson JM, Haas DW, DeBoer D, Christie M. The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty. J Arthroplasty. 1999;14:339–346.CrossRefPubMedGoogle Scholar
  14. 14.
    Krause W, Mathis RS. Fatigue properties of acrylic bone cement: a review. J Biomed Mater Res. 1988;22(3 Suppl):37–53.PubMedGoogle Scholar
  15. 15.
    Krause W, Mathis RS, Grimes LW. Fatigue properties of acrylic bone cement: S-N, P-N, and P-S-N data. J Biomed Mater Res. 1988;22(A2 Suppl):221–244.CrossRefPubMedGoogle Scholar
  16. 16.
    Kurtz SM, Villarraga ML, Zhao K, Edidin AA. Static and fatigue mechanical behavior of bone cement with elevated barium sulfate content for treatment of vertebral compression fractures. Biomaterials. 2005;26:3699–3712.CrossRefPubMedGoogle Scholar
  17. 17.
    Lewis G. Properties of acrylic bone cement: state-of-the-art review. J Biomed Mater Res. 1997;38:155–182.CrossRefPubMedGoogle Scholar
  18. 18.
    Lewis G. Fatigue testing and performance of acrylic bone cement: state-of-the-art review. J Biomed Mater Res. 2003;66:457–486.CrossRefGoogle Scholar
  19. 19.
    Lewis G, Bhattaram A. Influence of a pre-blended antibiotic (gentamicin sulphate powder) on various mechanical, thermal, and physical properties of three acrylic bone cements. J Appl Biomater. 2006;20:377–408.CrossRefGoogle Scholar
  20. 20.
    Lewis G, Janna S. Estimation of the optimum loading of an antibiotic powder in an acrylic bone cement. Acta Orthop. 2006;77:622–627.CrossRefPubMedGoogle Scholar
  21. 21.
    Lewis G, Janna S, Bhattaram A. Influence of the method of blending an antibiotic powder with an acrylic bone cement powder on physical, mechanical, and thermal properties of the cured cement. Biomaterials. 2005;26:4317–4325.CrossRefPubMedGoogle Scholar
  22. 22.
    Lewis G, Li Y. Dependence of in vitro fatigue properties of PMMA bone cement on the polydispersity index of its powder. J Mech Behav Biomed Mater. 2009;3:94–101.CrossRefPubMedGoogle Scholar
  23. 23.
    Livermore DM. Future directions with daptomycin. J Antimicrob Chemother. 2008;62(Suppl 3):iii41–iii49.Google Scholar
  24. 24.
    Merkhan IK, Hasenwinkel JM, Gilbert JL. Gentamicin release from two-solution and powder-liquid poly(methyl methacrylate)-based bone cements by using novel pH method. J Biomed Mater Res. 2004;69A:577–583.CrossRefGoogle Scholar
  25. 25.
    Persson C, Baleani M, Guandalini L, Tigani D, Viceconti M. Mechanical effects of the use of vancomycin and meropenem in acrylic bone cement. Acta Orthop. 2006;77:617–621.CrossRefPubMedGoogle Scholar
  26. 26.
    Richelsoph KC, Webb ND, Haggard WO. Elution behavior of daptomycin-loaded calcium sulfate pellets: a preliminary study. Clin Orthop Relat Res. 2007;461:68–73.PubMedGoogle Scholar
  27. 27.
    Schittkowski K. NLPQL: a Fortran subroutine solving constrained nonlinear programming problems. Annals Oper Res. 1986;5:485–500.Google Scholar
  28. 28.
    Shackelford JF. Introduction to Materials Science for Engineers. 6th ed. Upper Saddle River, NJ: Pearson Prentice Hall; 2005.Google Scholar
  29. 29.
    Steenbergen JN, Alder J, Thorne GM, Tally FP. Daptomycin: a lipopeptide antibiotic for the treatment of serious gram-positive infections. J Antimicrob Chemother. 2005;55:283–288.CrossRefPubMedGoogle Scholar
  30. 30.
    Thorne G, Alder J. Daptomycin: a novel lipopeptide antibiotic. Clin Microbiol News. 2002;24:33–40.CrossRefGoogle Scholar
  31. 31.
    Trampuz A, Widmer AF. Infections associated with orthopedic implants. Curr Opin Infect Dis. 2006;19:349–356.CrossRefPubMedGoogle Scholar
  32. 32.
    van de Belt H, Neut D, Schenk W, van Horn JR, van der Mei HC, Busscher HJ. Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand. 2000;71:625–629.CrossRefPubMedGoogle Scholar
  33. 33.
    Webb ND, McCanless JD, Courtney HS, Bumgardner JD, Haggard WO. Daptomycin eluted from calcium sulfate appears effective against Staphylococcus. Clin Orthop Relat Res. 2008;466:1383–1387.CrossRefPubMedGoogle Scholar
  34. 34.
    Youngman JR, Ridgway GL, Haddad FS. Antibiotic-loaded cement in revision joint replacement. Hosp Med. 2003;64:613–616.PubMedGoogle Scholar

Copyright information

© The Association of Bone and Joint Surgeons® 2010

Authors and Affiliations

  • Gladius Lewis
    • 1
  • Jennifer L. Brooks
    • 2
    Email author
  • Harry S. Courtney
    • 3
  • Yuan Li
    • 1
  • Warren O. Haggard
    • 2
  1. 1.Department of Mechanical EngineeringThe University of MemphisMemphisUSA
  2. 2.Department of Biomedical EngineeringThe University of MemphisMemphisUSA
  3. 3.Veterans Affairs Medical Center and Department of MedicineUniversity of Tennessee Health Science CenterMemphisUSA

Personalised recommendations