Mecikoglu Mete, Saygi Baransel, Yildirim Yakup, Karadag-Saygi Evrim, Ramadan Saime Sezgin, Esemenli Tanil
Animal Research Laboratory, Marmara University School of Medicine, Istanbul, Turkey.
J Bone Joint Surg Am. 2006 Jun;88(6):1208-14. doi: 10.2106/JBJS.E.00007.
Infection around an implanted orthopaedic device is a devastating complication, and the treatment of infections involving slime-forming bacteria is especially difficult. The purpose of the present study was to evaluate the effectiveness of a proteolytic enzyme, serratiopeptidase, in the eradication of a periprosthetic infection in an in vivo animal model.
In sixty Sprague-Dawley rats, the medullary canal of the right femur was drilled through the intercondylar notch and was inoculated with a Staphylococcus epidermidis strain (ATCC 35984) with a high slime-producing capacity. The cavity was filled with polymethylmethacrylate cement, and a Kirschner wire that had contact with the knee joint was inserted. None of the animals received any treatment for two weeks. Twenty rats were killed at two weeks after the inoculation in order to determine if the infection had become established. The remaining forty rats were randomized into two groups. One group received serratiopeptidase enzyme injections into the knee joint in addition to antibiotic therapy for four weeks, and the other group received intra-articular saline solution injections together with the same antibiotic therapy. The animals from both groups were killed two weeks after the end of therapy (on Day 56). The knee specimens were evaluated bacteriologically and histologically to determine the prevalence of persistent infection and the effects of the enzyme on local tissue.
At two weeks, inoculated bacteria grew on culture of specimens from twelve (63.2%) of nineteen animals in the no-treatment group. Microbiological testing suggested that infection persisted in only one (5.6%) of eighteen animals in the serratiopeptidase-and-antibiotic group, whereas it was present in six (37.5%) of sixteen animals in the antibiotic-only group (p = 0.001). Histological evaluation showed similar results (kappa = 0.92).
Serratiopeptidase was effective for eradicating infection caused by biofilm-forming bacteria in this experimental animal model. The antibiofilm property of the enzyme may enhance antibiotic efficacy in the treatment of staphylococcal infections.
植入式骨科器械周围感染是一种严重的并发症,治疗涉及产黏液细菌的感染尤其困难。本研究的目的是评估一种蛋白水解酶——沙雷氏菌肽酶在体内动物模型中根除假体周围感染的有效性。
在60只Sprague-Dawley大鼠中,通过髁间切迹钻通右股骨的髓腔,并接种具有高产黏液能力的表皮葡萄球菌菌株(ATCC 35984)。髓腔内填充聚甲基丙烯酸甲酯骨水泥,并插入一根与膝关节接触的克氏针。两周内所有动物均未接受任何治疗。接种两周后处死20只大鼠,以确定感染是否已确立。其余40只大鼠随机分为两组。一组在接受四周抗生素治疗的同时,膝关节内注射沙雷氏菌肽酶,另一组在接受相同抗生素治疗的同时,关节内注射生理盐水。治疗结束两周后(第56天)处死两组动物。对膝关节标本进行细菌学和组织学评估,以确定持续感染的发生率以及该酶对局部组织的影响。
两周时,未治疗组19只动物中有12只(63.2%)的标本培养出接种的细菌。微生物学检测表明,沙雷氏菌肽酶联合抗生素组18只动物中只有1只(5.6%)存在持续感染,而仅用抗生素组16只动物中有6只(37.5%)存在持续感染(p = 0.001)。组织学评估显示了类似的结果(kappa = 0.92)。
在该实验动物模型中,沙雷氏菌肽酶对根除生物膜形成细菌引起的感染有效。该酶的抗生物膜特性可能会增强抗生素在治疗葡萄球菌感染中的疗效。