Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, 382 West Street Road, Kennett Square, PA 19348, Philadelphia,
Eur Cell Mater. 2022 Feb 2;43:6-21. doi: 10.22203/eCM.v043a03.
Orthopaedic surgical site infections, especially when a hardware is involved, are associated with biofilm formation. Clinical strategies for biofilm eradication still fall short. The present study used a novel animal model of long-bone fixation with vancomycin- or gentamicin-controlled release and measured the levels of antibiotic achieved at the site of release and in the surrounding tissue. Then, using fluids that contain serum proteins (synovial fluid or diluted serum), the levels of vancomycin or gentamicin required to substantially reduce colonising bacteria were measured in a model representative of either prophylaxis or established biofilms. In the in vivo model, while the levels immediately adjacent to the antibiotic release system were up to 50× the minimal inhibitory concentration in the first 24 h, they rapidly dropped. At peripheral sites, values never reached these levels. In the in vitro experiments, Staphylococcus aureus biofilms formed in serum or in synovial fluid showed a 5-10 fold increase in antibiotic tolerance. Importantly, concentrations required were much higher than those achieved in the local delivery systems. Finally, the study determined that the staged addition of vancomycin and gentamicin was not more efficacious than simultaneous vancomycin and gentamicin administration when using planktonic bacteria. On the other hand, for biofilms, the staged addition seemed more efficacious than adding the antibiotics simultaneously. Overall, data showed that the antibiotics' concentrations near the implant in the animal model fall short of the concentrations required to eradicate biofilms formed in either synovial fluid or serum.
骨科手术部位感染，特别是涉及植入物时，与生物膜形成有关。目前用于消除生物膜的临床策略仍然存在不足。本研究使用新型长骨固定动物模型，采用万古霉素或庆大霉素控释，并测量释放部位和周围组织中的抗生素浓度。然后，使用含有血清蛋白（滑液或稀释血清）的液体，测量预防或已建立生物膜模型中所需的万古霉素或庆大霉素浓度，以显著减少定植细菌。在体内模型中，尽管紧邻抗生素释放系统的水平在最初 24 小时内高达最小抑菌浓度的 50 倍，但它们迅速下降。在周围部位，这些水平从未达到这些水平。在体外实验中，金黄色葡萄球菌生物膜在血清或滑液中形成时，抗生素的耐受性增加了 5-10 倍。重要的是，所需浓度远高于局部递送系统中达到的浓度。最后，该研究确定，与同时给予万古霉素和庆大霉素相比，分阶段添加万古霉素和庆大霉素对浮游菌的疗效并不更好。另一方面，对于生物膜，分阶段添加似乎比同时添加抗生素更有效。总体而言，数据表明，动物模型中植入物附近的抗生素浓度低于消除在滑液或血清中形成的生物膜所需的浓度。
