The In Vitro Elution Characteristics Of Antibiotic-carried Calcium Sulfate Bone Substitutes, And Treatment Of The Use Of Vancomycin-carried Calcium Sulfate In Open Fracture

Objective: To investigate the in vitro elution characteristics of antibiotic-carriedcalcium sulfate beads. And evaluate the use of a Vancomycin-carried Sulfate Calcium bonesubstitutes in the treatment of open fracture.Methods: The study was divided three parts: The in vitro soak of antibiotic-carriedCalcium Sulfate. The in vitro elution characteristics of antibiotic-carried Calcium Sulfate.The clinic use of a Vancomycin-carried Sulfate Calcium bone substitutes.The in vitro soak of antibiotic-carried Calcium Sulfate: Four artificial bone calciumsulfate powders, were separately mixed with the four antibiotics: Vancomycin500mg,50mg tobramycin,600mg teicoplanin,240mg gentamicin, then adding solvents. Ifcondensed, we can get some white antibiotic-carried Calcium Sulfate Beads. The packagedcalcium sulfate beads with vancomycin, tobramycin, teicoplanin and gentamicin were thengas sterilized. The beads were placed in phosphate-buffered saline and kept at36°C for6weeks. The soaking trial has two separate series of assays which were run simultaneouslyfor both types of beads. In one assay, a bead containing vancomycin was placed in a freshvial of phosphate buffered saline after each assay. The same was done with beadscontaining tobramycin, teicoplanin and gentamicin. In the second series of assays,9vialsof phosphate buffered saline each containing1vancomycin bead and9vials of phosphatebuffered saline each containing1tobramycin bead,9vials of phosphate buffered salineeach containing1teicoplanin bead,9vials of phosphate buffered saline each containing1gentamicin bead were arranged, The phosphate-buffered saline was then assayed atpredetermined times for both the four antibiotics bead series. A high performance1iquidchromatography(HPLC) method was used to determine the concentration of vancomycinand teicoplanin in the phosphate-buffered saline. Color reactions of Evans blue withaminoglycoside antibiotics was used to determine the concentration of tobramycin andgentamicin in the phosphate-buffered saline.The use of calcium sulfate carried with vancomycin in the treatment of open fractures:thirteen patients (10men,3women) who sustained open fractures of long bones wereenrolled. Mean patient age was35.8years (range,23-56years). According to theclassification system developed by Gustilo and Anderson, there were10type II openfractures,3type IIIa open fractures. All the patients were treated withvancomycin-impregnanted calcium sulfate and internal/external fixation. Clinical signs ofwound infection were recorded. Postoperative radiographs were used to evaluate the bone healing and absorption process.Result: The amount of teicoplanin and tobramycin assayed nearly equaled thecalculated amount of antibiotic per bead measured before bead construction. Also, a largeproportion of the elution of vancomycin and teicoplanin from the calcium sulfate was mosswithin one week. The elution of tobramycin from the calcium sulfate was complete within2week. The elution of gentamicin from the calcium sulfate was complete within a week.Clinic researches suggests that twelve of13patients were followed-up successfully, withan average follow-up of8months (range,5-11months). No infection was present in the12patients. Bone union was observed in all the patients, with a mean bone union time of3.4months (range,4-9months). All the calcium sulfate pellets had completely resorbed inan average of2months (range,1-3months).Conclusion: The results of this study show that vancomycin, tobramycin andteicoplanin can be eluted over a short period of time from the antibiotic-carried sulfatecalcium bone substitutes and remain stable concentrations in vitro. but that may notcorrelate clinically in vivo. Further studies need to be performed in vivo to better evaluatecalcium sulfate as an effective material to deliver antibiotics in a consistent and predictablemanner. Our study showed that the combination of internal/external fixation and calciumsulfate carried with vancomycin could decrease the incidence of deep infection withoutimpairment to the bone healing process in the treatment of open fractures of long bones.