Modeling of Daptomycin Release from Medium-Dose Daptomycin-Xylitol-Loaded PMMA Bone Cements

Abstract

Antibiotic-loaded poly (methyl methacrylate) bone cements (ALPBCs) are widely used as an agent to decrease the occurrence of periprosthetic joint infection (PJI). Most often, the antibiotic used in an ALPBC is gentamicin, tobramycin, or vancomycin. In many recent clinical studies, it has been reported that the pathogens that commonly present in PIJ are becoming resistant to these antibiotics. As such, a new generation of antibiotics is emerging, among which is daptomycin. Literature reports with a clinically relevant medium-dose daptomycin-loaded cement show that the daptomycin release rate from cylindrical specimens is low. Incorporation of a poragen, such as dextrose, glycine, or particulate xylitol, into the cement powder has been shown to be an effective way to increase daptomycin release rate. There are, however, no studies on modeling of daptomycin release from specimens of either a daptomycin-loaded cement or a daptomycin-poragen-loaded cement. In the present work, we determine the profiles of daptomycin release from cylindrical medium-dose daptomycin-xylitol-loaded cement specimens, as a function of the particulate xylitol loading. We used these results and relationships that have been shown to model antibiotic release from ALPBC specimens to obtain the best-fit relationship for the present cements. Through this approach, we demonstrated that, regardless of the xylitol loading, the daptomycin release profile is a mixture of initial burst followed by a slow Fickian diffusion.