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

Abstract

The rate of release of an antibiotic from an antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is low. This may be increased by adding a particulate poragen (eg, xylitol) to the cement powder. However, the appropriate poragen amount is unclear. We explored the appropriate amount of xylitol to use in a PMMA bone cement loaded with daptomycin and xylitol. We prepared four groups of cement, each comprising the same amount of daptomycin in the powder (1.36g/40g dry powder) but different amounts of xylitol (0, 0.7, 1.4, and 2.7g); the xylitol mass ratio (X) (mass divided by mass of the final dry cement-daptomycin-xylitol mixture) ranged from 0 to 6.13 wt/wt%. Eight mechanical, antibiotic release, and bacterial inhibitory properties were determined using three to 22 specimens or replicates per test. We then used an optimization method to determine an appropriate value of X by (1) identifying the best-fit relationship between the value of each property and X, (2) defining a master objective function incorporating all of the best fits; and (3) determining the value of X at the maximum master objective function. We found an appropriate xylitol amount to be 4.46 wt/wt% (equivalent to 1.93g xylitol mixed with 1.36g daptomycin and 40g dry cement powder). We demonstrated a method that may be used to determine an appropriate xylitol amount for a daptomycin-xylitol-loaded PMMA bone cement. These findings will require in vivo confirmation. While we identified an appropriate amount of xylitol in a daptomycin-xylitol-loaded PMMA bone cement as a prophylactic agent in total joint arthroplasties, clinical evaluations are needed to confirm the effectiveness of this cement.