Mäkinen T J, Veiranto M, Knuuti J, Jalava J, Törmälä P, Aro H T
Department of Orthopaedic Surgery and Traumatology, Orthopaedic Research Unit, University of Turku, FIN-20520, Turku, Finland.
Bone. 2005 Feb;36(2):292-9. doi: 10.1016/j.bone.2004.11.009.
Impregnation of antimicrobial agents within biodegradable orthopedic implants provides a possibility for local antimicrobial prophylaxis of biomaterial-related infections. The objective of this study was to evaluate the efficacy of a bioabsorbable ciprofloxacin containing bone screw (Ab-PLGA) in the prevention of biomaterial-related infection due to Staphylococcus aureus in a rabbit model. Animals in Group I (n=8) received a Ab-PLGA screw contaminated with S. aureus, while animals in Group II (n=8) received a stainless steel (SS) screw contaminated with S. aureus. In two negative control groups, the animals received a Ab-PLGA screw (Group III, n=4) or a SS screw (Group IV, n=4) without bacterial contamination. 18F-FDG-PET imaging, performed at 6 weeks, was applied as a novel quantitative in vivo imaging modality of implant-related infection. Infection was verified by swab cultures, direct cultures of the retrieved implant, and quantitative cultures of pulverized bone. The concentrations of ciprofloxacin in serum and local bone tissue were determined by a high performance liquid chromatographic (HPLC) method with fluorescence (FLD) detection. In the group of contaminated Ab-PLGA screws, all cultures were negative. In the group of contaminated SS screws, all cultures of retrieved implants and six cultures out of eight of pulverized bone were positive for inoculated S. aureus. In negative control groups, all cultures were negative except one contaminant (S. cohnii) found in a SS screw culture. Verified infection of contaminated SS screws was collaborated by the increased 18F-FDG-PET uptake (P=0.004 compared with the group of contaminated Ab-PLGA screws). The mean bone tissue concentration of ciprofloxacin varied from 2.54 to 0.83 microg/g bone as a function of distance from the implantation site. The serum concentration of ciprofloxacin remained undetectable and below the resolution of the analytic method (<5.0 ng/ml). This study confirmed the in vivo efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to S. aureus.
在可生物降解的骨科植入物中浸渍抗菌剂为局部预防与生物材料相关的感染提供了一种可能。本研究的目的是在兔模型中评估含生物可吸收环丙沙星的骨螺钉（Ab-PLGA）预防金黄色葡萄球菌引起的与生物材料相关感染的效果。第一组（n=8）动物接受被金黄色葡萄球菌污染的Ab-PLGA螺钉，而第二组（n=8）动物接受被金黄色葡萄球菌污染的不锈钢（SS）螺钉。在两个阴性对照组中，动物分别接受未被细菌污染的Ab-PLGA螺钉（第三组，n=4）或SS螺钉（第四组，n=4）。在6周时进行的18F-FDG-PET成像被用作一种新型的与植入物相关感染的体内定量成像方式。通过拭子培养、取出的植入物的直接培养以及粉碎骨的定量培养来验证感染情况。采用高效液相色谱（HPLC）荧光（FLD）检测法测定血清和局部骨组织中环丙沙星的浓度。在被污染的Ab-PLGA螺钉组中，所有培养均为阴性。在被污染的SS螺钉组中，取出的植入物的所有培养以及八份粉碎骨培养中的六份对接种的金黄色葡萄球菌呈阳性。在阴性对照组中，除了在一个SS螺钉培养中发现一种污染物（科氏葡萄球菌）外，所有培养均为阴性。被污染的SS螺钉经证实的感染通过18F-FDG-PET摄取增加得到佐证（与被污染的Ab-PLGA螺钉组相比，P=0.004）。环丙沙星在骨组织中的平均浓度随距植入部位的距离而变化，范围为2.54至0.83微克/克骨。血清中环丙沙星的浓度仍未检测到且低于分析方法的检测限（<5.0纳克/毫升）。本研究证实了含生物可吸收抗生素的骨螺钉在预防金黄色葡萄球菌引起的与生物材料相关感染方面的体内疗效。
