The elution of antibiotics from hand mixed antibiotic-laden polymethylmethacrylate (PMMA) must be increased to achieve clinical performance equivalent to commercially manufactured antibiotic beads (not available in the USA) in the management of musculoskeletal infections. Adding fillers such as glycine and dextran to polymethylmethacrylate increases the elution of antibiotics from antibiotic-laden PMMA. We propose xylitol, a naturally occurring sweetener with direct antibiofilm properties, as a filler material. To compare the efficacy of xylitol and glycine as fillers on the elution of antibiotics from PMMA, elution studies were performed on mixtures of Palacos polymethylmethacrylate and daptomycin (1 gm) with xylitol or glycine as the filler (28 g). Xylitol and glycine enhanced the daptomycin activity eluted from the polymethylmethacrylate. Xylitol was more effective than glycine, having a greater increase in daptomycin release at all data points; on day one xylitol increased the elution of daptomycin 2.67 times whereas glycine increased it 1.78 times also on day one. The eluant concentration of daptomycin remained higher longer for xylitol; 3.90 microg/mL for xylitol versus 2.25 microg/mL for glycine on day 9. Xylitol is inexpensive and readily available. It can be hand mixed with PMMA, and is more effective than glycine as a filler to enhance daptomycin release. Considering possible antibiofilm activity, xylitol may be a more advantageous choice.