Sakaguchi Hisashi, Marui Akira, Hirose Keiichi, Nomura Takamasa, Arai Yoshio, Bir Shyamal Chandra, Huang Yuhong, Esaki Jiro, Tabata Yasuhiko, Ikeda Tadashi, Komeda Masashi
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Thorac Cardiovasc Surg. 2008 Jan;135(1):25-31. doi: 10.1016/j.jtcvs.2007.06.027.
Methicillin-resistant Staphylococcus aureus graft infection is one of the most serious complications of vascular surgery. Vancomycin is a potent antibiotic against methicillin-resistant S. aureus; however, systemic administration of vancomycin is not very effective against methicillin-resistant S. aureus graft infection. Therefore, we investigated whether a local sustained release of vancomycin prevents methicillin-resistant S. aureus graft infection.
We have developed a poly-L-lactide-co-caprolactone sheet that enabled sustained release of vancomycin for 2 weeks. An expanded polytetrafluoroethylene vascular graft patch (1.5 mm2) was sutured at the anterior wall of the incised murine abdominal aorta. Methicillin-resistant S. aureus (1.0 x 10(3) colony-forming units) was inoculated onto the graft surface. Thereafter, the graft was treated as follows (n = 6 each): no treatment (control group), local injection of an aqueous solution of vancomycin (vancomycin solution group) and local implantation of poly-L-lactide-co-caprolactone containing vancomycin (vancomycin-PLCA group). After 7 days, the graft and blood were sampled and cultured.
The methicillin-resistant S. aureus counts in the grafts of the vancomycin-PLCA group were significantly lower than those of the other groups. Blood cultures of the vancomycin-PLCA group were all negative, whereas those of the other groups were all positive for infection. The survival rate in the vancomycin-PLCA group at 28 days was considerably higher than that in the control group (83.3% vs 16.7%).
A local sustained-release sheet containing vancomycin reduced methicillin-resistant S. aureus counts in the infected vascular grafts, prevented sepsis, and drastically improved survival rates. This can be used as a highly effective and less-invasive adjunctive treatment method for preventing prosthetic methicillin-resistant S. aureus graft infection.
耐甲氧西林金黄色葡萄球菌移植感染是血管外科最严重的并发症之一。万古霉素是一种强效抗耐甲氧西林金黄色葡萄球菌的抗生素；然而，全身应用万古霉素对耐甲氧西林金黄色葡萄球菌移植感染的疗效不佳。因此，我们研究了万古霉素局部缓释是否能预防耐甲氧西林金黄色葡萄球菌移植感染。
我们研制了一种聚左旋丙交酯-乙交酯共聚物片，可使万古霉素持续释放2周。将一片扩张型聚四氟乙烯血管移植补片（1.5平方毫米）缝合于切开的小鼠腹主动脉前壁。将耐甲氧西林金黄色葡萄球菌（1.0×10³菌落形成单位）接种于移植补片表面。此后，对移植补片进行如下处理（每组n = 6）：不处理（对照组）、局部注射万古霉素水溶液（万古霉素溶液组）和局部植入含万古霉素的聚左旋丙交酯-乙交酯共聚物（万古霉素-PLCA组）。7天后，采集移植补片和血液样本进行培养。
万古霉素-PLCA组移植补片中耐甲氧西林金黄色葡萄球菌数量显著低于其他组。万古霉素-PLCA组的血培养均为阴性，而其他组的血培养均为感染阳性。万古霉素-PLCA组28天的生存率显著高于对照组（83.3%对16.7%）。
含万古霉素的局部缓释片可减少感染血管移植补片中耐甲氧西林金黄色葡萄球菌数量，预防败血症，并显著提高生存率。这可作为一种高效、微创的辅助治疗方法，用于预防耐甲氧西林金黄色葡萄球菌人工血管移植感染。
