Cai Xun-Zi, Yan Shi-Gui, Wu Hao-Bo, He Rong-Xin, Dai Xue-Song, Chen Hai-Xiang, Yan Rui-Jian, Zhao Xin-Hua
Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Jiefang Road 88, Hangzhou 310009, People's Republic of China.
Antimicrob Agents Chemother. 2007 Sep;51(9):3199-204. doi: 10.1128/AAC.01465-06. Epub 2007 Jul 9.
This study sought to investigate the effect of delayed pulsed-wave ultrasound with low frequency on drug release from and the antimicrobial efficacy of vancomycin-loaded acrylic bone cement in vivo and the possible mechanism of this effect. After the implantation of cement and the inoculation of Staphylococcus aureus into the bilateral hips of rabbits, ultrasound (average intensity, 300 mW/cm(2); frequency, 46.5 kHz; on/off ratio, 20 min/10 min) was applied to animals in the normal ultrasound group (UG(0-12)) from 0 through 12 h after surgery and to those in the delayed-ultrasound group (UG(12-24)) from 12 through 24 h after surgery. The control group (CG) was not exposed to ultrasound. Based on vancomycin concentrations in left hip cavities at projected time intervals, the amount of time during which the local drug concentration exceeded the MIC (T(>MIC)) in UG(12-24) was significantly prolonged compared with that in either CG or UG(0-12), and the ratios between the areas under the concentration-time curves over 24 h and the MIC for UG(0-12) and UG(12-24) were both increased compared with that for CG. The greatest reductions in bacterial densities in both right hip aspirates and right femoral tissues at 48 h were achieved with UG(12-24). Local hemorrhage in rabbits of UG(0-12) during the 12-h insonation was more severe than that in rabbits of UG(12-24). Of four variables, the T(>MIC) and the bioacoustic effect were both identified as parameters predictive of the enhancement of the antimicrobial efficacy of cement by ultrasound. Sustained concentrations above the MIC replaced early high maximum concentrations and long-term subtherapeutic release of the drug, provided that ultrasound was not applied until local hemorrhage was relieved. The enhancement of the antimicrobial efficacy of cement by ultrasound may be attributed to the prolonged T(>MIC) and the bioacoustic effect caused by ultrasound.
本研究旨在探讨低频延迟脉冲波超声对体内万古霉素负载丙烯酸骨水泥药物释放及抗菌效果的影响以及这种影响的可能机制。在兔双侧髋关节植入骨水泥并接种金黄色葡萄球菌后，正常超声组（UG(0 - 12)）在术后0至12小时接受超声治疗（平均强度，300 mW/cm²；频率，46.5 kHz；开/关比，20分钟/10分钟），延迟超声组（UG(12 - 24)）在术后12至24小时接受超声治疗。对照组（CG）未接受超声治疗。根据预计时间间隔时左髋关节腔万古霉素浓度，UG(12 - 24)组局部药物浓度超过最低抑菌浓度（T(>MIC)）的时间显著长于CG组或UG(0 - 12)组，与CG组相比，UG(0 - 12)组和UG(12 - 24)组24小时浓度 - 时间曲线下面积与最低抑菌浓度的比值均增加。UG(12 - 24)组在48小时时右髋关节吸出物和右股骨组织中的细菌密度降低最为显著。UG(0 - 12)组在12小时超声照射期间兔子的局部出血比UG(12 - 24)组的兔子更严重。在四个变量中，T(>MIC)和生物声学效应均被确定为超声增强骨水泥抗菌效果的预测参数。只要在局部出血缓解后才应用超声，高于最低抑菌浓度的持续浓度就会取代早期的高最大浓度和药物的长期亚治疗释放。超声增强骨水泥抗菌效果可能归因于超声导致的T(>MIC)延长和生物声学效应。
