VANCOMYCIN-ELUTING ULTRA-HIGH MOLECULAR WEIGHT POLYETHYLENE TO TREAT PERIPROSTHETIC JOINT INFECTIONS

O. Muratoglu, V. Suhardi, D. Bichara, Sheldon J. J. Kwok, A. Freiberg, H. Rubash, S. Yun, E. Oral
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引用次数: 0

Abstract

Introduction About 2% of primary total joint replacement arthroplasty (TJA) procedures become infected. Periprosthetic joint infection (PJI) is currently one of the main reasons requiring costly TJA revisions, posing a burden on patients, physicians and insurance companies. 1 Currently used drug-eluting polymers such as bone cements offer limited drug release profiles, sometimes unable to completely clear out bacterial microorganisms within the joint space. For this study we determined the safety and efficacy of an antibiotic-eluting UHMWPE articular surface that delivered local antibiotics at optimal concentrations to treat PJI in a rabbit model. Materials and Methods Skeletally mature adult male New Zealand White rabbits received either two non-antibiotic eluting UHMWPE (CONTROL, n=5) or vancomycin-eluting UHMWPE (TEST, n=5) (3 mm in diameter and 6 mm length) in the patellofemoral groove ( Fig. 1 ). All rabbits received a beaded titanium rod in the tibial canal (4 mm diameter and 12 mm length). Both groups received two doses of 5 × 10 7 cfu of bioluminescent S. aureus (Xen 29, PerkinElmer 119240) in 50 µL 0.9 % saline in the following sites: (1) distal tibial canal prior to insertion of the rod; (2) articular space after closure of the joint capsule ( Fig. 1 ). None of the animals received any intravenous antibiotics for this study. Bioluminescence signal (photons/second) was measured when the rabbits expired, or at the study endpoint (day 21). The metal rods were stained with BacLight ® Bacterial Live-Dead Stain and imaged using two-photon microscopy to detect live bacteria. Hardware, polyethylene implants and joint tissues were sonicated to further quantify live bacteria via plate seeding. Results All control rabbits expired within 7 days ( Fig. 2a). One rabbit in the test group expired at day 7 and another at day 15. All control rabbits had positive bioluminescence (live bacteria), while none of the test rabbits did (Fig 2b). Kidney (creatinine and BUN) and liver functions (ALT and ALP) remained normal for all rabbits. All control rabbits showed positive bacterial culture after sonication, while all test rabbits were negative. Two-photon imaging showed 75±10 % viability for bacteria adhered to the metal rods in the control and no viability in the test group. Discussion This rabbit model showed that vancomycin eluted from UHMWPE is sufficient to eradicate S. aureus in joint space and in between the bone-implant interface of tibial canal. One limitation of this study is the lack of intravenous antibiotic treatment, which is standard clinical practice. In addition, joint infections are often associated with already formed biofilms, which were not tested in this study. However, safety data (normal kidney and liver functions) and complete eradication of S. aureus is an encouraging finding. Conclusion Vancomycin-eluting UHMWPE effectively eliminated bacteria in a rabbit model of acute peri-prosthetic joint infection. This material is promising as a replacement liner to treat joint infections in revision surgery. For any figures or tables, please contact authors directly (see Info & Metrics tab above).
万古霉素洗脱超高分子量聚乙烯治疗假体周围关节感染
约2%的原发性全关节置换术(TJA)手术会感染。假体周围关节感染(PJI)是目前需要昂贵的TJA修改的主要原因之一,给患者、医生和保险公司带来了负担。目前使用的药物洗脱聚合物如骨水泥提供有限的药物释放,有时不能完全清除关节空间内的细菌微生物。在这项研究中,我们确定了抗生素洗脱UHMWPE关节表面的安全性和有效性,该关节表面以最佳浓度局部递送抗生素治疗兔模型PJI。材料和方法骨骼成熟的成年雄性新西兰大白兔在髌股沟内接受两种非抗生素洗脱的超高分子量聚乙烯(CONTROL, n=5)或万古霉素洗脱的超高分子量聚乙烯(TEST, n=5)(直径3mm,长度6mm)(图1)。所有家兔在胫骨管内置入一根直径为4mm、长度为12mm的串珠钛棒。两组患者均在以下部位注射了两剂5 × 10 7 cfu的生物发光金黄色葡萄球菌(Xen 29, PerkinElmer 119240),浸在50µL 0.9%生理盐水中:(1)在插入棒之前,胫骨远端管;(2)关节囊闭合后的关节间隙(图1)。在这项研究中,所有动物都没有接受任何静脉注射抗生素。生物发光信号(光子/秒)在兔子过期时或研究终点(第21天)测量。用BacLight®细菌活死染色剂对金属棒进行染色,并用双光子显微镜成像检测活菌。对硬件、聚乙烯植入物和关节组织进行超声处理,通过平板播种进一步量化活菌。结果所有对照兔均在7天内死亡(图2a)。试验组1只于第7天死亡,另1只于第15天死亡。所有对照兔都有阳性生物发光(活细菌),而所有试验兔都没有(图2b)。肾脏(肌酐和BUN)和肝功能(ALT和ALP)均保持正常。对照兔超声培养均为阳性,试验兔超声培养均为阴性。双光子成像结果显示,粘附在金属棒上的细菌存活率为75±10%,试验组细菌存活率为零。该家兔模型表明,从UHMWPE中洗脱的万古霉素足以根除关节间隙和胫骨管骨-种植体界面之间的金黄色葡萄球菌。这项研究的一个局限性是缺乏静脉注射抗生素治疗,这是标准的临床实践。此外,关节感染通常与已经形成的生物膜有关,这在本研究中没有进行测试。然而,安全性数据(肾脏和肝脏功能正常)和金黄色葡萄球菌的完全根除是一个令人鼓舞的发现。结论万古霉素洗脱的超高分子量聚乙烯能有效消除兔急性假体周围关节感染模型中的细菌。这种材料是有希望的替代衬垫治疗关节感染翻修手术。对于任何数字或表格,请直接联系作者(见上面的信息和指标标签)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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