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用于非骨水泥型假体的利福平-磷霉素涂层:对甲氧西林敏感金黄色葡萄球菌(MSSA)和耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌作用

Rifampicin-fosfomycin coating for cementless endoprostheses: antimicrobial effects against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA).

作者信息

Alt Volker, Kirchhof Kristin, Seim Florian, Hrubesch Isabelle, Lips Katrin S, Mannel Henrich, Domann Eugen, Schnettler Reinhard

机构信息

Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany; Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany.

Biomet Deutschland GmbH, 14167 Berlin, Germany.

出版信息

Acta Biomater. 2014 Oct;10(10):4518-24. doi: 10.1016/j.actbio.2014.06.013. Epub 2014 Jun 16.

DOI:10.1016/j.actbio.2014.06.013
PMID:24948548
Abstract

New strategies to decrease infection rates in cementless arthroplasty are needed, especially in the context of the growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections. The purpose of this study was to investigate the antimicrobial activity of a rifampicin-fosfomycin coating against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA in a rabbit infection prophylaxis model. Uncoated or rifampicin-fosfomycin-coated K-wires were inserted into the intramedullary canal of the tibia in rabbits and contaminated with an inoculation dose of 10(5) or 10(6) colony-forming units of MSSA EDCC 5055 in study 1 and MRSA T6625930 in study 2, respectively. After 28days the animals were killed and clinical, histological and microbiological assessment, including pulse-field gel electrophoresis, was conducted. Positive culture growth in agar plate testing and/or clinical signs and/or histological signs were defined positive for infection. Statistical evaluation was performed using Fisher's exact test. Both studies showed a statistically significant reduction of infection rates for rifampicin-fosfomycin-coated implants compared to uncoated K-wires (P=0.015). In both studies none of the 12 animals that were treated with a rifampicin-fosfomycin-coated implant showed clinical signs of infection or a positive agar plate testing result. In both studies, one animal of the coating group showed the presence of sporadic bacteria with concomitant inflammatory signs in histology. The control groups in both studies exhibited an infection rate of 100% with clear clinical signs of infection and positive culture growth in all animals. In summary, the rifampicin-fosfomycin-coating showed excellent antimicrobial activity against both MSSA and MRSA, and therefore warrants further clinical testing.

摘要

需要新的策略来降低非骨水泥型关节成形术中的感染率,尤其是在耐甲氧西林金黄色葡萄球菌(MRSA)感染发病率不断上升的背景下。本研究的目的是在兔感染预防模型中研究利福平-磷霉素涂层对甲氧西林敏感金黄色葡萄球菌(MSSA)和MRSA的抗菌活性。在研究1中,将未涂层或利福平-磷霉素涂层的克氏针插入兔胫骨骨髓腔,并分别用10(5)或10(6)个MSSA EDCC 5055菌落形成单位接种剂量进行污染;在研究2中,用MRSA T6625930进行污染。28天后处死动物,并进行临床、组织学和微生物学评估,包括脉冲场凝胶电泳。琼脂平板试验中的阳性培养生长和/或临床体征和/或组织学体征被定义为感染阳性。使用Fisher精确检验进行统计学评估。两项研究均显示,与未涂层的克氏针相比,利福平-磷霉素涂层植入物的感染率有统计学意义的降低(P=0.015)。在两项研究中,接受利福平-磷霉素涂层植入物治疗的12只动物中,没有一只出现感染的临床体征或琼脂平板试验阳性结果。在两项研究中,涂层组的一只动物在组织学上显示存在散在细菌并伴有炎症体征。两项研究中的对照组感染率均为100%,所有动物均有明显的感染临床体征和阳性培养生长。总之,利福平-磷霉素涂层对MSSA和MRSA均显示出优异的抗菌活性,因此值得进一步进行临床试验。

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