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浸渍妥布霉素和万古霉素的骨移植体可高浓度递送抗生素,以预防通常与人工关节感染相关的细菌。

Bone allograft impregnated with tobramycin and vancomycin delivers antibiotics in high concentrations for prophylaxis against bacteria commonly associated with prosthetic joint infections.

作者信息

Berglund Björn, Wezenberg Daphne, Nilsson Maud, Söderquist Bo, Nilsson Lennart E, Schilcher Jörg

机构信息

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.

出版信息

Microbiol Spectr. 2024 Oct 23;12(12):e0041424. doi: 10.1128/spectrum.00414-24.

Abstract

Local delivery of antibiotics as prophylaxis for prosthetic joint infections (PJIs) is frequently used during total hip replacement surgery. Morselized bone allograft impregnated with vancomycin and tobramycin () could provide effective prophylaxis against bacteria commonly associated with PJIs. In this study, the concentrations of antibiotics released by bone allograft impregnated with were determined by using an bioassay system entailing measuring inhibition zone diameters caused by antibiotic-impregnated bone chips cast in agar against standard curves. The concentrations were determined in samples of -impregnated bone graft taken before and after the application of the bone graft in the patients undergoing acetabular revision surgery. Antibiotic-impregnated bone grafts, sampled prior to application in the patient, delivered antibiotics in the concentration ranges of 730-9,800 mg/L for tobramycin and 1,300-11,000 mg/L for vancomycin. Samples taken after application in the patient released lower concentrations of tobramycin (490-1,900 mg/L; < 0.01) and vancomycin (3,000-5,100 mg/L; < 0.05); however, these concentrations remained well above the tobramycin minimum inhibitory concentrations (MICs) for investigated, highly tobramycin-resistant strains (MICs > 256 mg/L). At the tested concentrations, bone graft material mixed with delivered antibiotics in potent concentrations above the MICs for bacteria causing PJIs. Clinical trials are needed to evaluate the efficacy and risk of -impregnated bone graft as a prophylactic agent for patients undergoing hip replacement surgery.IMPORTANCEAntibiotic prophylaxis is the cornerstone of successful joint replacement surgery, reducing the risk for the dreaded complication of prosthetic joint infection (PJI) to roughly 0.5%-2% in standard total hip replacement (THR). In addition to systemic antibiotics, antibiotics added locally have the potential to reduce the PJI risk even further, because of the high concentrations that can be achieved in the joint with limited risk for systemic toxicity. The results in the current study show that bone chips impregnated with a combination of tobramycin and vancomycin () release antibiotics in concentrations that are potent against common bacteria causing PJIs. Especially in high-risk patients, our results support the prophylactic use of in hip replacement surgery requiring the use of a bone graft. A clinical study testing the efficacy of -impregnated bone graft in reducing the incidence of PJI in hip replacement surgery is currently ongoing (EudraCT: 2021-001708-14).

摘要

在全髋关节置换手术中,局部使用抗生素预防人工关节感染(PJI)是常用的方法。浸渍有万古霉素和妥布霉素( )的碎骨同种异体移植骨可有效预防与PJI常见相关的细菌。在本研究中,通过使用一种生物测定系统来确定浸渍有 的骨同种异体移植骨释放的抗生素浓度,该系统需要测量琼脂中由浸渍抗生素的骨芯片形成的抑菌圈直径,并对照标准曲线进行测定。在接受髋臼翻修手术的患者应用骨移植前后,对浸渍有 的骨移植样本进行了浓度测定。在患者应用前采集的浸渍抗生素的骨移植样本中,妥布霉素的释放浓度范围为730 - 9800 mg/L,万古霉素为1300 - 11000 mg/L。在患者应用后采集的样本中,妥布霉素(490 - 1900 mg/L; < 0.01)和万古霉素(3000 - 5100 mg/L; < 0.05)的释放浓度较低;然而,这些浓度仍远高于所研究的对妥布霉素高度耐药的 菌株的妥布霉素最低抑菌浓度(MICs)(MICs > 256 mg/L)。在测试浓度下,与 混合的骨移植材料释放的抗生素浓度高于引起PJI的细菌的MICs。需要进行临床试验来评估浸渍有 的骨移植作为髋关节置换手术患者预防剂的疗效和风险。重要性抗生素预防是成功进行关节置换手术的基石,在标准全髋关节置换(THR)中,可将可怕的人工关节感染(PJI)并发症风险降低至约0.5% - 2%。除了全身使用抗生素外,局部添加抗生素有可能进一步降低PJI风险,因为在关节中可达到高浓度且全身毒性风险有限。本研究结果表明,浸渍有妥布霉素和万古霉素组合( )的骨芯片释放的抗生素浓度对引起PJI的常见细菌有效。特别是在高危患者中,我们的结果支持在需要使用骨移植的髋关节置换手术中预防性使用 。一项测试浸渍有 的骨移植在降低髋关节置换手术中PJI发生率方面疗效的临床研究正在进行中(欧洲临床试验注册号:2021 - 001708 - 14)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd2/11619462/b80186a74de6/spectrum.00414-24.f001.jpg

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