Calcium Phosphate Cement loaded with 10% vancomycin delivering high early and late local antibiotic concentration in vitro

Abstract

Background: Antibiotics impregnated calcium phosphate cement (CPC) has emerged as a local treatment of osteomyelitis. However, there is no study investigating the optimal concentrations of vancomycin (VCM) included in CPC to obtain prolonged drug release (≥8 weeks) and also with enough compressive strength (>the normal cancellous bone, 11MPa) for osteomyelitis therapy. Therefore, we bring forward two questions: 1) Was antibiotic activity of the eluates correlated to the load of antibiotics within the cement? 2) Were the mechanical properties of CPC affected by VCM-loading?

Hypothesized: There was an optimal concentrations of vancomycin (VCM) loaded in CPC which could provide sufficient effective antibacterial time (≥8 weeks) and enough compressive strength (>11MPa).

Materials and methods: CPC specimens were obtained by incorporating different doses (weigh ratios of 0%, 5%, 10%, 15%, 20%, 25 and 30%) of injectable VCM into CPC. The antibacterial effect of released VCM solution against Staphylococcus aureus was assessed by inhibition ring assays. The physicochemical properties such as compressive strengths were characterized and compared among these specimens.

Results: Drug release profiles showed only 5 and 10% VCM-loaded CPC displayed a long enough drug release time (at least 8 weeks) and maintained the eluate concentrations (>4μg/mL) with effective antibacterial ability. The concentration of VCM in 10% group at 8th week was twice higher than 5% group. Compressive strength test showed that the proportional increase of VCM/CPC ratios resulted in a significant decrease of compressive strength (r=-0.906, p<0.001).

Conclusion: 10% VCM-loaded CPC offered the optimal physicochemical properties and drug releasing profile and appears as the most suitable concentration for clinical use.

Level of evidence: III.

Keywords: Calcium phosphate cement; Mechanical strength; Osteomyelitis therapy; Vancomycin.