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

  • Symposium: Papers Presented at the 2009 Meeting of the Musculoskeletal Infection Society
  • Published:
Clinical Orthopaedics and Related Research®

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.

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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.

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, The University of Memphis, Memphis, TN, USA

    Gladius Lewis PhD & Yuan Li PhD

  2. Department of Biomedical Engineering, The University of Memphis, Memphis, TN, USA

    Jennifer L. Brooks BS & Warren O. Haggard PhD

  3. Veterans Affairs Medical Center and Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    Harry S. Courtney PhD

Authors
  1. Gladius Lewis PhD
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  2. Jennifer L. Brooks BS
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  3. Harry S. Courtney PhD
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  4. Yuan Li PhD
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  5. Warren O. Haggard PhD
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Corresponding author

Correspondence to Jennifer L. Brooks BS.

Additional information

The institution of one or more of the authors (WOH, GL) has received funding from Cubist Pharmaceuticals, Inc (Lexington, MA). Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

This work was performed at The University of Memphis and Veterans Affairs Medical Center.

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Lewis, G., Brooks, J.L., Courtney, H.S. et al. An Approach for Determining Antibiotic Loading for a Physician-directed Antibiotic-loaded PMMA Bone Cement Formulation. Clin Orthop Relat Res 468, 2092–2100 (2010). https://doi.org/10.1007/s11999-010-1281-0

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  • DOI: https://doi.org/10.1007/s11999-010-1281-0

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