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. 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 MethodsDaptomycin 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 daptomycinloaded 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.

Evaluation of Two Sources of Calcium Sulfate for a Local Drug Delivery System: A Pilot Study

“…However, the total percent release of daptomycin from the naturally sourced CaSO 4 pellets was higher and the concentration of daptomycin released on Day 1 was lower than previously reported (Table 3) [22,27]. The initial daptomycin released from the naturally sourced and synthetic calcium sulfate pellets is closer to initial antibiotics eluted from PMMA beads (Table 3) [13,14,19]. An explanation for the higher total release of the antibiotic could be the result of faster elution to measurement activities in comparison to previous studies.…”

Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm

“…Unlike PMMA, which requires secondary removal through surgical procedures, phosphatidylcholine coatings are degradable and materials have been used in orthopaedic applications [26]. Through application to the surface directly, more coverage of the potentially contaminated implant site is provided compared with antibiotic-loaded beads or sponges [34,67,70,76]. Interestingly, we observed some inhibitory effect of unloaded phosphatidylcholine on biofilm formation in vitro, which may be a result of the hydrophobic nature of the coating [21].…”

A Daptomycin-Xylitol-loaded Polymethylmethacrylate Bone Cement: How Much Xylitol Should Be Used?

“…Several studies have reported the in vitro properties of either low-dose daptomycin-loaded PMMA bone cement (B 1 g daptomycin per 40 g cement powder [13]) [5,14,26] or a higher-dose variant (C 2 g) [5,14,26,41]. These reports show the daptomycin release profile in phosphatebuffered saline (PBS) solution at 37°C is characterized by a burst followed by a period of slow decrease [5,14,26].…”

“…These reports show the daptomycin release profile in phosphatebuffered saline (PBS) solution at 37°C is characterized by a burst followed by a period of slow decrease [5,14,26]. At relatively low amounts (up to 7.5% of the mass of the dry cement powder-daptomycin mixture), daptomycin exerts a marginal influence on the cement's fatigue limit, tensile strength, yield strength, compressive strength, and compressive modulus (compared to the value for a cement that did not contain the antibiotic) [14,26,41], but with a higher amount of daptomycin (11 wt/wt%), there is an appreciable drop in the cement's fatigue limit [26].…”

“…These reports show the daptomycin release profile in phosphatebuffered saline (PBS) solution at 37°C is characterized by a burst followed by a period of slow decrease [5,14,26]. At relatively low amounts (up to 7.5% of the mass of the dry cement powder-daptomycin mixture), daptomycin exerts a marginal influence on the cement's fatigue limit, tensile strength, yield strength, compressive strength, and compressive modulus (compared to the value for a cement that did not contain the antibiotic) [14,26,41], but with a higher amount of daptomycin (11 wt/wt%), there is an appreciable drop in the cement's fatigue limit [26]. There is a sizeable literature on methods to improve the release profile of antibiotics from ALABC cylinders, including incorporation of a particulate filler (such as lactose, mesoporous silica nanoparticles, or xylitol) in the cement powder [9,37,43] and subjection of cured cement specimens to continuous or intermittent watt-level lowfrequency ultrasound [3].…”