Long-term antibacterial activity of vancomycin from calcium phosphate cement in vivo

Abstract

BACKGROUND: Periprosthetic joint infection is a major complication of total joint arthroplasty, with treatment requiring a two-stage exchange procedure and 6 weeks of systemic antibiotics. However, depending on the infection site, intravenous delivery of antibiotics like vancomycin (VCM) can have poor tissue transferability, thus reducing their therapeutic effect. OBJECTIVE: This study demonstrates the 24-week in vivo release profile and antibacterial activity of VCM from calcium phosphate cement impregnated with VCM (CPC/VCM) and compares them with those from polymethylmethacrylate impregnated with VCM (PMMA/VCM). METHODS: Rats were implanted with the test specimens between the fascia and quadriceps. After implantation for 24 weeks, the test specimens were removed and residual VCM was extracted to calculate the concentration of VCM released into rat tissues. We also examined the antibacterial activity of releasable VCM from the removed test specimens by placing them directly onto the surface of agar. RESULTS: CPC/VCM released greater concentrations of VCM for a longer period of time within the 24 weeks than PMMA/VCM. Moreover, CPC/VCM released 1.4 to 26.1-fold more VCM than PMMA/VCM. Using Staphylococcus aureus, antibacterial activity was logarithmically correlated with VCM concentration across the entire concentration range tested (12.5–800 μg/mL). While the area within which inhibition was observed—the inhibition zone—for both CPC/VCM and PMMA/VCM formed and gradually shrank with time after implantation, that for CPC/VCM was significantly larger than that for PMMA/VCM in each week after implantation. CONCLUSION: CPC/VCM releases greater amounts of VCM with antibacterial activity for longer periods of time than PMMA/VCM, suggesting that CPC is effective for facilitating the release of antibiotics for local action in patients with established postoperative infection.