Pförringer D, Obermeier A, Kiokekli M, Büchner H, Vogt S, Stemberger A, Burgkart R, Lucke M
Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Unfallchirurgie, Munich, Germany
Klinikum rechts der Isar, Technische Universität München, Klinik für Orthopädie und Sportorthopädie, Munich, Germany.
Antimicrob Agents Chemother. 2016 Jun 20;60(7):3897-905. doi: 10.1128/AAC.00080-16. Print 2016 Jul.
Substitution of bones is a well-established, necessary procedure to treat bone defects in trauma and orthopedic surgeries. For prevention or treatment of perioperative infection, the implantation of resorbable bone substitute materials carrying antibiotics is a necessary treatment. In this study, we investigated the newly formulated calcium-based resorbable bone substitute materials containing either gentamicin (CaSO4-G [Herafill-G]), vancomycin (CaSO4-V), or tobramycin (Osteoset). We characterized the released antibiotic concentration per unit. Bone substitute materials were implanted in bones of rabbits via a standardized surgical procedure. Clinical parameters and levels of the antibiotic-releasing materials in serum were determined. Local concentrations of antibiotics were measured using antimicrobial tests of bone tissue. Aminoglycoside release kinetics in vitro per square millimeter of bead surface showed the most prolonged release for gentamicin, followed by vancomycin and, with the fastest release, tobramycin. In vivo level in serum detected over 28 days was highest for gentamicin at 0.42 μg/ml, followed by vancomycin at 0.11 μg/ml and tobramycin at 0.04 μg/ml. The clinical parameters indicated high biocompatibility for materials used. None of the rabbits subjected to the procedure showed any adverse reaction. The highest availability of antibiotics at 14.8 μg/g on day 1 in the cortical tibia ex vivo was demonstrated for gentamicin, decreasing within 14 days. In the medulla, vancomycin showed a high level at 444 μg/g on day 1, decreasing continuously over 14 days, whereas gentamicin decreased faster within the initial 3 days. The compared antibiotic formulations varied significantly in release kinetics in serum as well as locally in medulla and cortex.
骨替代是治疗创伤和骨科手术中骨缺损的一种成熟且必要的手术。为预防或治疗围手术期感染，植入携带抗生素的可吸收骨替代材料是一种必要的治疗方法。在本研究中，我们研究了新配制的含钙可吸收骨替代材料，其中含有庆大霉素（硫酸钙-G [Herafill-G]）、万古霉素（硫酸钙-V）或妥布霉素（Osteoset）。我们对每单位释放的抗生素浓度进行了表征。通过标准化手术程序将骨替代材料植入兔骨中。测定了临床参数和血清中抗生素释放材料的水平。使用骨组织抗菌试验测量局部抗生素浓度。每平方毫米珠粒表面的氨基糖苷类抗生素体外释放动力学显示，庆大霉素释放时间最长，其次是万古霉素，释放最快的是妥布霉素。在28天内检测到的血清体内水平，庆大霉素最高，为0.42μg/ml，其次是万古霉素，为0.11μg/ml，妥布霉素为0.04μg/ml。临床参数表明所用材料具有高生物相容性。接受该手术的兔子均未出现任何不良反应。庆大霉素在第1天离体胫骨皮质中的抗生素最高可用性为14.8μg/g，在14天内下降。在骨髓中，万古霉素在第1天显示出高水平，为444μg/g，在14天内持续下降，而庆大霉素在最初3天内下降更快。所比较的抗生素制剂在血清以及骨髓和皮质局部的释放动力学上有显著差异。
