关键词: drug delivery periprosthetic joint infections pharmacokinetic modeling of antibiotics polymeric delivery devices

Mesh : Humans Anti-Bacterial Agents / pharmacology therapeutic use Polymethyl Methacrylate / chemistry Molecular Weight Prosthesis-Related Infections / etiology microbiology Polyethylenes / pharmacology Bone Cements / pharmacology

来  源:   DOI:10.1002/mabi.202300389   PDF(Pubmed)

Abstract:
The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load-bearing solution and needs to be replaced by a functional implant. Elution from the ultrahigh molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo-gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug-loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra-articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least 3 weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 h, showing that a small fraction of the implant surface loaded with antibiotics may be sufficient against Staphylococci.
摘要:
全关节置换后假体周围感染(PJI)的发生对患者和医疗保健系统构成了巨大的负担。在抗生素治疗期间,负载抗生素的聚甲基丙烯酸甲酯(PMMA)骨水泥通常用于临时间隔物。PMMA不是承重解决方案,需要用功能性植入物代替。从用于药物递送的超高分子量聚乙烯(UHMWPE)承载表面的洗脱可以将功能性与临床相关剂量的抗生素的释放相结合。在这项研究中,研究了将一系列抗生素掺入UHMWPE的可行性。通过热重分析和核磁共振波谱评估药物稳定性。通过压缩成型制备载药UHMWPE,在不同的负荷下使用八种抗生素。从UHMWPE洗脱的药物的预测关节内浓度高于对葡萄球菌的最低抑制浓度至少3周,是PJI的主要致病菌。在72小时内,在体外覆盖2%的代表性膝盖植入物的样品中确认了抗菌功效,表明植入物表面负载有抗生素的一小部分可能足以对抗葡萄球菌。
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