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抗生素涂层锁定钢板治疗感染性骨不连的抗菌机制及制备

Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions.

作者信息

Wagner Robert Kaspar, Guarch-Pérez Clara, van Dam Alje P, Zaat Sebastian Aj, Kloen Peter

机构信息

Department of Orthopedic Surgery and Sports Medicine, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9; Amsterdam Movement Sciences, Musculoskeletal Health, Amsterdam, The Netherlands.

Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location University of Amsterdam, Meibergdreef 9, The Netherlands.

出版信息

Strategies Trauma Limb Reconstr. 2023 May-Aug;18(2):73-81. doi: 10.5005/jp-journals-10080-1586.

Abstract

BACKGROUND

Antibiotic-impregnated cement-coated plates (ACPs) have been used successfully for temporary internal fixation between stages in the two-stage treatment of infected non-unions. We describe our approach of using an ACP in the staged treatment of a methicillin-resistant (MRSA)-infected distal femoral non-union below a total hip prosthesis. In addition, we present the results of an experiment to provide an in-depth insight into the capacity of ACPs in (i) treating residual biofilm and (ii) preventing bacterial recolonisation.

MATERIALS AND METHODS

In the first stage, we used a titanium LISS plate coated with hand-mixed PALACOS with vancomycin (PAL-V) for temporary internal fixation combined with commercially prepared COPAL with gentamicin and vancomycin (COP-GV) to fill the segmental defect. In the second stage, the non-union was treated with double-plate fixation and bone grafting.A Kirby-Bauer agar disc diffusion assay was performed to determine the antimicrobial activity of both ACPs and a drug-release assay to measure antibiotic release over time. A biofilm killing assay was also carried out to determine if the antibiotic released was able to reduce or eradicate biofilm of the patient's MRSA strain.

RESULTS

At one-year follow-up, there was complete bone-bridging across the previous non-union. The patient was pain-free and ambulatory without need for further surgery. Both ACPs with COP-GV and PAL-V exerted an antimicrobial effect against the MRSA strain with peak concentrations of antibiotic released within the first 24 hours. Concentrations released from COP-GV in the first 24 hours caused a 7.7-fold log reduction of colony-forming units (CFU) in the biofilm. At day 50, both COP-GV and PAL-V still released concentrations of antibiotic above the respective minimal inhibitory concentrations (MIC), likely contributing to the positive clinical outcome.

CONCLUSION

The use of an ACP provides stability and infection control in the clinical scenario of an infected non-union. This is confirmed where the release of antibiotics from ACPs is characterised by an early burst followed by a prolonged sustained release above the MIC until 50 days. The burst release from COP-GV reduces CFU in the biofilm and prevents early recolonisation through synergistic activity of the released vancomycin and gentamicin.

CLINICAL SIGNIFICANCE

An antibiotic-impregnated cement-coated plate is a useful addition to the surgeon's armamentarium to provide temporary internal fixation without the disadvantages of external fixation and contribute to infection control in an infected non-union.

HOW TO CITE THIS ARTICLE

Wagner RK, Guarch-Pérez C, van Dam AP, . Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions. Strategies Trauma Limb Reconstr 2023;18(2):73-81.

摘要

背景

抗生素浸渍骨水泥涂层钢板(ACPs)已成功用于感染性骨不连两阶段治疗中阶段间的临时内固定。我们描述了在全髋关节置换术下方的耐甲氧西林(MRSA)感染的股骨远端骨不连的分期治疗中使用ACP的方法。此外,我们展示了一项实验结果,以深入了解ACP在(i)治疗残留生物膜和(ii)防止细菌再定植方面的能力。

材料与方法

在第一阶段,我们使用涂有手工混合的含万古霉素的PALACOS(PAL-V)的钛制LISS钢板进行临时内固定,并结合商业制备的含庆大霉素和万古霉素的COPAL(COP-GV)填充节段性骨缺损。在第二阶段,采用双钢板固定和植骨治疗骨不连。进行Kirby-Bauer琼脂纸片扩散试验以确定两种ACP的抗菌活性,并进行药物释放试验以测量抗生素随时间的释放情况。还进行了生物膜杀灭试验,以确定释放的抗生素是否能够减少或根除患者MRSA菌株的生物膜。

结果

在一年的随访中,先前骨不连处实现了完全骨桥接。患者无痛且可走动,无需进一步手术。COP-GV和PAL-V两种ACP均对MRSA菌株发挥了抗菌作用,抗生素在最初24小时内释放达到峰值浓度。COP-GV在最初24小时内释放的浓度使生物膜中的菌落形成单位(CFU)对数减少了7.7倍。在第50天时,COP-GV和PAL-V仍释放出高于各自最低抑菌浓度(MIC)的抗生素浓度,这可能促成了良好的临床结果。

结论

在感染性骨不连的临床情况下,使用ACP可提供稳定性并控制感染。ACP释放抗生素的特点是早期爆发,随后在50天内持续释放高于MIC的浓度,这证实了上述结论。COP-GV的爆发式释放减少了生物膜中的CFU,并通过释放的万古霉素和庆大霉素的协同活性防止早期再定植。

临床意义

抗生素浸渍骨水泥涂层钢板是外科医生装备中的一项有用补充,可提供临时内固定,而无外固定的缺点,并有助于控制感染性骨不连中的感染。

如何引用本文

Wagner RK, Guarch-Pérez C, van Dam AP, . 抗生素浸渍骨水泥涂层锁定钢板在治疗感染性骨不连中的抗菌机制及制备. 《创伤肢体重建策略》2023;18(2):73 - 81.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21d2/10628616/589a79475cca/stlr-18-73-g001.jpg

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