Dalbavancin is thermally stable at clinically relevant temperatures against methicillin-sensitive Staphylococcus Aureus.

Abstract

Introduction: While the rate of orthopaedic infections has remained constant over the years, the burden on healthcare systems continues to rise with an aging population. Local antibiotic delivery via polymethyl methacrylate bone cement is a common adjunct in treating bone and joint infections. Dalbavancin is a novel lipoglycopeptide antibiotic in the same class as vancomycin that has shown efficacy against Gram-positive organisms when used systemically but has not been investigated as a local antibiotic. This study aims to identify whether dalbavancin is thermally stable at the temperatures expected during the polymerization of polymethyl methacrylate cement. Methods: Stock solutions of dalbavancin were prepared and heated using a polymerase chain reaction machine based upon previously defined models of curing temperatures in two clinically relevant models: a 10 mm polymethyl methacrylate bead and a polymethyl methacrylate articulating knee spacer model. Aliquots of heated dalbavancin were then transferred to be incubated at core body temperature (37 ${}^{\circ }$C) and analyzed at various time points up to 28 d. The minimum inhibitory concentration at which 90 % of colonies were inhibited (MIC${}_{90}$) for each heated sample was determined against methicillin-sensitive Staphylococcus aureus (American Type Culture Collection, ATCC, 0173K) using a standard microbroth dilution assay. Results: The average MIC${}_{90}$ of dalbavancin was 1.63 $\mu g{\mathrm{mL}}^{-1}$ $\pm 0.49$ against 0173K S. aureus. There were no significant differences in the relative MIC${}_{90}$ values after heating dalbavancin in either model compared to unheated control dalbavancin. Conclusions: Dalbavancin is thermally stable at the curing temperatures of polymethyl methacrylate cement and at human core body temperature over 28 d. Future in vitro and in vivo studies are warranted to further investigate the role of dalbavancin as a local antibiotic prior to its clinical use.