Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination antibiotic PMMA composite system composed of rifampicin-filled β-cyclodextrin (β-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through zone of inhibition, drug activity, antibiotic release, and refilling, as well as mechanical studies. Our combination antibiotic PMMA composite system achieved up to an 8-fold increase in the duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for load-bearing applications (e.g., bone cement), our composites are certainly amenable for a variety of nonload-bearing applications (e.g., antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).

中文翻译：

---

PMMA中的组合抗生素递送提供了持续的广谱抗菌活性，并允许在植入后进行补充。

外科医生通常将抗生素添加到聚甲基丙烯酸甲酯（PMMA）中，以局部治疗感染，例如在骨水泥中进行关节置换手术，以及植入式抗菌“珠子”。但是，这种策略在高危患者中价值有限，在高危患者中，感染可能是复发性或慢性的，否则很难治疗。另外，当仅掺入一种药物并用于多微生物感染（多种细菌）时，细菌就有可能产生抗生素耐药性。为了克服这些局限性，我们开发了一种组合抗生素PMMA复合系统，该系统由充满利福平的β-环糊精（β-CD）微粒添加到填充有第二种药物的PMMA中组成。通过抑制区域，药物活性，抗生素释放和补充来评估不同的制剂，以及力学研究。与临床使用的填充抗生素的PMMA相比，我们的组合抗生素PMMA复合材料系统的抗菌活性持续时间提高了8倍。包含CD微粒还允许在模拟植入后重新填充其他抗生素，从而产生更多的疗效窗口。力学测试表明，与未经修饰的对照相比，我们测试的制剂确实具有很小但显着的机械性能下降。尽管需要进一步的研究来确定测试的制剂是否仍然适合承重应用（例如骨水泥），但我们的复合材料肯定适合于多种非承重应用（例如，抗菌“珠子”）