title: An Approach for determining antibiotic loading for a physician-directed antibiotic-loaded PMMA bone cement formulation.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Mechanical Engineering, The University of Memphis, Memphis, TN, USA.
authors.forename: Gladius
authors.initials: G
authors.lastname: Lewis
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Brooks
authors.forename: Harry S
authors.initials: HS
authors.lastname: Courtney
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Warren O
authors.initials: WO
authors.lastname: Haggard
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D019643:Arthroplasty, Replacement / Q000379:methods; D001843:Bone Cements / Q000737:chemistry*; D017576:Daptomycin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D007595:Joint Prosthesis; D008422:Materials Testing; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D011208:Powders; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D004337:Drug Carriers; D004338:Drug Combinations; D011208:Powders; D019904:Polymethyl Methacrylate; D017576:Daptomycin