Shiels Stefanie M, Tennent David J, Akers Kevin S, Wenke Joseph C
Extremity Trauma and Regenerative Medicine Task Area, US Army Institute of Surgical Research, JBSA-Fort Sam Houston, TX, United States.
Extremity Trauma and Regenerative Medicine Task Area, US Army Institute of Surgical Research, JBSA-Fort Sam Houston, TX, United States; Department of Orthopaedics, San Antonio Military Medical Center (Brooke Army Medical Center), JBSA-Fort Sam Houston, TX, United States.
Injury. 2017 Oct;48(10):2095-2100. doi: 10.1016/j.injury.2017.08.021. Epub 2017 Aug 16.
Open fractures are often complicated by infection. In cases of severe soft tissue and vascular injury, systemic antibiotics may be ineffective due to their inability to reach and provide direct antimicrobial activity to the zone of injury. High antibiotic concentrations within the wound can be achieved with reduced systemic toxicity by using local antibiotic delivery. As bacteria associated with musculoskeletal injuries frequently form biofilms, antibiotic selection is important. Herein, the use of rifampin, an antibiotic with activity against biofilms, delivered via polymethylmethacrylate (PMMA) beads is evaluated for use in a traumatic musculoskeletal wound model.
PMMA beads loaded with rifampin, or combinations of rifampin and vancomycin, were prepared and evaluated for time to curing, drug release kinetics in vitro, and infection prevention in vivo using a well-established rat model of musculoskeletal infection. A segmental bone defect was created and contaminated with methicillin susceptible Staphylococcus aureus (UAMS-1). Wounds were debrided, irrigated, and treated with PMMA beads, containing rifampin or combinations of rifampin plus vancomycin, following a 6-h (early) or 24-h (delayed) treatment. After 14days, tissue, implants, and beads were removed for bacterial quantification and assessed for rifampin resistance.
There was a direct association between loaded concentration and release kinetics of the rifampin and vancomycin from PMMA beads. Higher rifampin concentrations delayed PMMA curing times. The addition of vancomycin to PMMA resulted in more rapid release of rifampin from beads. However, the highest concentration of rifampin loaded PMMA beads (10% wt/wt) was the only treatment to significantly reduce bacterial counts. No rifampin resistance was observed.
Although higher concentrations of rifampin resulted in significant reductions of bacteria, these levels extended PMMA curing times and transformed PMMA material characteristics. While these characteristics make the material unsuitable for weight-bearing applications, such as total joint arthroplasty, the use of rifampin-loaded PMMA beads may be an effective intervention in a contaminated traumatic extremity wound due to its ability to eradicate biofilms.
开放性骨折常并发感染。在严重软组织和血管损伤的情况下，全身使用抗生素可能无效，因为它们无法到达损伤区域并提供直接的抗菌活性。通过局部抗生素递送可以在降低全身毒性的情况下在伤口内实现高抗生素浓度。由于与肌肉骨骼损伤相关的细菌经常形成生物膜，抗生素的选择很重要。在此，评估了通过聚甲基丙烯酸甲酯（PMMA）珠递送的具有抗生物膜活性的抗生素利福平在创伤性肌肉骨骼伤口模型中的应用。
制备了负载有利福平或利福平和万古霉素组合的PMMA珠，并使用成熟的肌肉骨骼感染大鼠模型评估其固化时间、体外药物释放动力学和体内感染预防效果。创建节段性骨缺损并用甲氧西林敏感金黄色葡萄球菌（UAMS-1）污染。伤口清创、冲洗后，在6小时（早期）或24小时（延迟）治疗后用含有利福平或利福平加万古霉素组合的PMMA珠进行治疗。14天后，取出组织、植入物和珠子进行细菌定量，并评估利福平耐药性。
利福平和万古霉素从PMMA珠中的负载浓度与释放动力学之间存在直接关联。较高的利福平浓度会延迟PMMA固化时间。在PMMA中添加万古霉素会使利福平从珠子中释放得更快。然而，负载利福平的PMMA珠的最高浓度（10%重量/重量）是唯一能显著减少细菌数量的治疗方法。未观察到利福平耐药性。
虽然较高浓度的利福平可显著减少细菌数量，但这些水平延长了PMMA固化时间并改变了PMMA材料特性。虽然这些特性使该材料不适用于负重应用，如全关节置换术，但负载利福平的PMMA珠因其能够根除生物膜，可能是污染创伤性肢体伤口的有效干预措施。
