In Vitro Elution Characteristics of Vancomycin in a Composite Calcium Phosphate/Calcium Sulfate Bone Substitute

Abstract

Background: Periprosthetic joint infection is a particularly difficult orthopedic problem, complicating a growing number of revision procedures. Joint debridement and systemic antibiotics are the mainstay of treatment, yet difficulty remains in maintaining a minimum inhibitory concentration of antibiotic at the localized site of infection. Study Aims: This study analyzes the elution characteristics of a 40%bwt calcium phosphate-60%bwt calcium sulfate composite, at varying concentrations of vancomycin. Methods: Four groups of varying concentrations of vancomycin (2.63%bwt, 5.13%, 9.76%, and 17.78%) were mixed with one pack of the composite cement. At designated time intervals up to 28 days, the antibiotic concentration was detected using fluorescence polarization immunoassay and the elution trends compared. Results: The elution rate of each of the four groups decreased over time. At almost all of the intervals, the elution rates of the higher concentration groups were significantly higher than the lower concentration groups (P<0.05). Conclusions: Calcium sulfate reabsorbs over a prolonged period, producing porosity which allows for new bone ingrowth through occupation of osteoprogenitor cells and osteoblasts; while calcium phosphate acts as a long-term osteoconductive matrix. Clinical Relevance: The results of this study suggest that vancomycin can be mixed affectively with a calcium sulfate/ phosphate composite, both maintaining stability and eluting gradually over a clinically relevant period of time.

Limitation of the antibiotic‐eluting bone graft substitute: An example of gentamycin‐impregnated calcium sulfate

“…On the contrary, a high content of gentamycin in the calcium sulfate resulted in a high antibiotic release through the high concentration gradient. Similarly, Yang et al reported that the calcium phosphate/calcium sulfate bone substitute with a higher vancomycin content also had a higher elution rate than that of a lower vancomycin content sample . In spite of a dose‐dependent elution rate of gentamycin‐loaded calcium sulfate samples was noticed, all samples showed antibacterial activity and inhibited the growths of S. mutans efficiently even under low‐dose.…”

“…Previously, the influences of different antibiotics on the calcium sulfate were studied, and it was found that vancomycin, cefazolin, tobramycin, and amphotericin B extended setting time . Other studies reported that vancomycin did not influence the injectability and operability but changed the hydration progress and affected the in vivo absorption of calcium sulfate . However, the underlying mechanism for the influence of antibiotics on calcium sulfate remains unclear.…”

“…21 Other studies reported that vancomycin did not influence the injectability and operability but changed the hydration progress and affected the in vivo absorption of calcium sulfate. 22,23 However, the underlying mechanism for the influence of antibiotics on calcium sulfate remains unclear.…”

Effects of the addition of vancomycin on the physical and handling properties of calcium sulfate bone cement

“…The authors assumed that surfactant-induced modification of crystalline morphology and size distribution may have contributed to the increase in setting time. Moreover, it was found that the in vivo absorption of calcium sulfate was prolonged when vancomycin was added [22]. Although the addition of vancomycin did not influence the operability or injectability from a syringe, the antibiotic obviously influenced the hydration of calcium sulfate.…”

“…When a high amount of vancomycin was added to the calcium sulfate, the high concentration gradient caused a high antibiotic release. Yang et al demonstrated the elution characteristics of vancomycin in a composite calcium phosphate/calcium sulfate bone substitute, and also concluded that the elution rates of the higher concentration groups were significantly higher than those of the lower concentration groups [22]. Although the antibiotic-loaded calcium sulfate samples showed dose-dependent elution rates of vancomycin, no difference was observed in the zones of inhibition among groups which indicates that vancomycin inhibits the growths of S. aureus efficiently even under low-dose.…”