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当前综述——噬菌体作为治疗人工关节周围感染的独特治疗平台的兴起

Current review-The rise of bacteriophage as a unique therapeutic platform in treating peri-prosthetic joint infections.

作者信息

Akanda Zarique Z, Taha Mariam, Abdelbary Hesham

机构信息

Department of Surgery, Division of Orthopaedics, The Ottawa Hospital, Ottawa, Canada.

出版信息

J Orthop Res. 2018 Apr;36(4):1051-1060. doi: 10.1002/jor.23755. Epub 2017 Nov 22.

DOI:10.1002/jor.23755
PMID:28971508
Abstract

Peri-prosthetic joint infection (PJI) is one of the most serious and dreaded complications after total joint replacement (TJR). Due to an aging population and the constant rise in demand for TJR, the incidence of PJI is also increasing. Successful treatment of PJI is challenging and is associated with high failure rates. One of the main causes for treatment failure is bacterial biofilm formation on implant surfaces and the adherence of biofilm bacteria on tissue and bone next to the implant. Biofilms are protective shields to bacterial cells and possess many unique properties that leads to antibiotic resistance. New therapeutic platforms are currently being explored to breakdown biofilm matrix in order to enhance the efficacy of antibiotics. Bacteriophages (phages) is one of these unique therapeutic platforms that can degrade biofilms as well as target the killing of bacterial cells. Preclinical studies of biofilm-mediated infections have demonstrated the ability of phage to eradicate biofilms and clear infections by working synergistically with antibiotics. There is strong preclinical evidence that phage can reduce the concentration of antibiotics required to treat an infection. These findings support a promising role for phages as a future clinical adjunct to antibiotics. In addition, phage therapy can be personalized to target a specific bacterial strain. Clinical studies using phage therapy are limited in Western literature; but phase I studies have established good safety profile with no adverse outcomes reported. In order to translate phage therapy to treat PJI in clinics, further preclinical testing is still required to study optimal delivery methods as well as the interaction between phage and the immune system in vivo. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1051-1060, 2018.

摘要

人工关节周围感染(PJI)是全关节置换术(TJR)后最严重且令人恐惧的并发症之一。由于人口老龄化以及对TJR的需求持续上升,PJI的发病率也在增加。成功治疗PJI具有挑战性,且失败率很高。治疗失败的主要原因之一是植入物表面形成细菌生物膜以及生物膜细菌在植入物旁的组织和骨上黏附。生物膜是细菌细胞的保护屏障,具有许多导致抗生素耐药性的独特特性。目前正在探索新的治疗平台以破坏生物膜基质,从而提高抗生素的疗效。噬菌体是这些独特的治疗平台之一,它既能降解生物膜,又能靶向杀灭细菌细胞。生物膜介导感染的临床前研究已证明噬菌体能够通过与抗生素协同作用来根除生物膜并清除感染。有强有力的临床前证据表明噬菌体可降低治疗感染所需的抗生素浓度。这些发现支持噬菌体作为未来抗生素临床辅助手段的前景。此外,噬菌体疗法可针对特定细菌菌株进行个性化治疗。西方文献中使用噬菌体疗法的临床研究有限;但I期研究已证实其安全性良好,未报告不良后果。为了将噬菌体疗法转化应用于临床治疗PJI,仍需要进一步的临床前测试来研究最佳给药方法以及噬菌体与体内免疫系统之间的相互作用。© 2017骨科学研究协会。由威利期刊公司出版。《矫形外科学研究》36:1051 - 1060,2018年。

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