Tøttrup Mikkel, Bue Mats, Koch Janne, Jensen Louise Kruse, Hanberg Pelle, Aalbæk Bent, Fuursted Kurt, Jensen Henrik Elvang, Søballe Kjeld
Department of Orthopaedic Surgery (M.T. and K.S.) and Orthopaedic Research Unit (M.T., M.B., P.H., and K.S.), Aarhus University Hospital, Aarhus, Denmark Department of Orthopaedic Surgery, Horsens Regional Hospital, Horsens, Denmark.
Departments of Experimental Medicine (J.K.) and Veterinary Disease Biology (L.K.J., B.A., and H.E.J.), University of Copenhagen, Copenhagen, Denmark.
J Bone Joint Surg Am. 2016 Mar 2;98(5):363-9. doi: 10.2106/JBJS.O.00550.
The prolonged antibiotic therapy that is often needed for successful management of osteomyelitis may be related to incomplete penetration of antibiotics into the target site. The objective of this study was to assess the effects of implant-associated osteomyelitis on cefuroxime penetration into bone.
Implant-associated osteomyelitis using a Staphylococcus aureus strain was induced in the right tibia in ten pigs. After five days and following administration of 1500 mg of cefuroxime, measurements of cefuroxime were obtained using microdialysis for eight hours in the implant-related bone cavity, in the adjacent infected cancellous bone and infected subcutaneous tissue, and in healthy cancellous bone and subcutaneous tissue in the contralateral leg. Measurements of the corresponding free plasma concentrations were also obtained. The extent of the infection was assessed by postmortem computed tomography (CT) scans and cultures of blood, swabs, and bone specimens.
Bone destruction was found in the implant cavities. No structural bone changes in the adjacent infected cancellous bone were visible on CT scans. S. aureus was grown on culture of specimens from all implant cavities and from eight of ten swabs and seven of ten bone samples from the infected bone. The areas under the concentration-time curves for the different tissues differed significantly, with the lowest area under the curve found in the implant cavity (analysis of variance; p < 0.001). Although not as notable as for the implant cavity, cefuroxime penetration into infected cancellous bone was incomplete but comparable with that in healthy bone. Despite poorer tissue penetration, slightly increased time with concentrations above the minimal inhibitory concentration (MIC) was achieved in the implant cavity up to MICs of 2 mg/L compared with the other tissues, but the time was shorter for higher MICs.
Cefuroxime penetration into infected cancellous bone was incomplete but comparable with that in healthy bone. The destructive bone processes associated with acute osteomyelitis reduced cefuroxime penetration further.
These findings support the general clinical perception that fast diagnosis and early initiation of antibiotics before the development of implant-associated cavities is important in nonsurgical management of acute osteomyelitis.
成功治疗骨髓炎通常需要长期使用抗生素，这可能与抗生素在靶部位的穿透不完全有关。本研究的目的是评估植入物相关骨髓炎对头孢呋辛渗入骨骼的影响。
在10头猪的右胫骨中诱发使用金黄色葡萄球菌菌株的植入物相关骨髓炎。五天后，在给予1500mg头孢呋辛后，使用微透析在植入物相关的骨腔、相邻的感染松质骨和感染的皮下组织以及对侧腿部的健康松质骨和皮下组织中测量头孢呋辛8小时。还获得了相应的游离血浆浓度测量值。通过死后计算机断层扫描（CT）扫描以及血液、拭子和骨标本的培养来评估感染程度。
在植入物腔中发现了骨质破坏。CT扫描未发现相邻感染松质骨有结构性骨变化。金黄色葡萄球菌在所有植入物腔以及来自感染骨的10个拭子中的8个和10个骨样本中的7个的标本培养中生长。不同组织的浓度 - 时间曲线下面积差异显著，植入物腔中的曲线下面积最低（方差分析；p < 0.001）。虽然不如植入物腔明显，但头孢呋辛渗入感染松质骨不完全，但与健康骨中的情况相当。尽管组织穿透性较差，但与其他组织相比，在植入物腔中，当最低抑菌浓度（MIC）达到2mg/L时，浓度高于MIC的时间略有增加，但对于更高的MIC，时间较短。
头孢呋辛渗入感染松质骨不完全，但与健康骨中的情况相当。与急性骨髓炎相关的破坏性骨过程进一步降低了头孢呋辛的渗入。
这些发现支持了一般临床认识，即在非手术治疗急性骨髓炎中，在植入物相关腔隙形成之前快速诊断并早期使用抗生素很重要。
