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.
Highlights
There is no consensus on the incidence of periprosthetic joint infection (PJI) in total joint replacements, with values ranging from 40% for revisions [2], it is universally acknowledged that PJI is a major, if not intractable, problem
Only daptomycin has been incorporated in a PMMA bone cement and reported in some in vitro studies [20]-[25] and only daptomycin and telavancin have been used in PJI treatment [18] [19]
Each of the release kinetics models provided a very good fit to the experimental M-versus-t results, Equations (1) and (4) suffer from the fact that neither contains a term that could be associated with initial burst of the daptomycin (a phenomenon that is in clear display—see Figure 3(a) and Figure 3(b))
Summary
There is no consensus on the incidence of periprosthetic joint infection (PJI) in total joint replacements, with values ranging from 40% for revisions [2], it is universally acknowledged that PJI is a major, if not intractable, problem. To reduce the likelihood of PJI, antibiotic-loaded poly (methyl methacrylate) (PMMA) bone cements (ALPBCs) are widely used as a prophylaxis agent in primary cases or a treatment option in certain types of revision cases, such as second-stage reconstructions [7] [8]. For the former cases, there are a large number of approved low-dose commercially-available brands of these cements [7] [8]. A low-dose is defined as antibiotic loading of 1 g of antibiotic mixed with 40 g of dry cement powder [7]. Only daptomycin has been incorporated in a PMMA bone cement and reported in some in vitro studies [20]-[25] and only daptomycin and telavancin have been used in PJI treatment [18] [19]
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