An approach for determining antibiotic loading for a physician-directed antibiotic-loaded PMMA bone cement formulation

Gladius Lewis, Jennifer L. Brooks, Harry Courtney, Yuan Li, Warren O. Haggard

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2092-2100
Number of pages9
JournalClinical Orthopaedics and Related Research
Volume468
Issue number8
DOIs
StatePublished - Jan 1 2010

Fingerprint

Bone Cements
Daptomycin
Polymethyl Methacrylate
Anti-Bacterial Agents
Physicians
Powders
Knee Replacement Arthroplasties
Arthroplasty
Fatigue
Hip
Growth

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

An approach for determining antibiotic loading for a physician-directed antibiotic-loaded PMMA bone cement formulation. / Lewis, Gladius; Brooks, Jennifer L.; Courtney, Harry; Li, Yuan; Haggard, Warren O.

In: Clinical Orthopaedics and Related Research, Vol. 468, No. 8, 01.01.2010, p. 2092-2100.

Research output: Contribution to journalArticle

Lewis, Gladius ; Brooks, Jennifer L. ; Courtney, Harry ; Li, Yuan ; Haggard, Warren O. / An approach for determining antibiotic loading for a physician-directed antibiotic-loaded PMMA bone cement formulation. In: Clinical Orthopaedics and Related Research. 2010 ; Vol. 468, No. 8. pp. 2092-2100.
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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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