Samara E, Moriarty T F, Decosterd L A, Richards R G, Gautier E, Wahl P
AO Research Institute Davos, Davos, Switzerland.
AO Research Institute Davos, Davos, Switzerland
Bone Joint Res. 2017 May;6(5):296-306. doi: 10.1302/2046-3758.65.BJR-2017-0276.R1.
Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.
In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.
The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions.
This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. 2017;6:296-306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1.
热稳定性是决定抗生素制剂在骨科感染局部治疗中适用性的关键特性。尽管长期治疗是新型局部给药载体的既定目标，但描述长期热稳定性的数据稀缺，且骨科文献中缺乏避免特定载体材料干扰的研究。
在本研究中，共38种常用抗生素制剂在37°C的盐溶液中保存，在六周内评估其降解情况和抗菌活性。还测试了模拟放热固化骨水泥的初始补充热暴露的影响，因为这种材料常用作局部给药载体。抗生素降解通过液相色谱-质谱联用或适当的免疫测定进行评估。随时间的抗菌活性通过 Kirby-Bauer 纸片扩散法测定。
模拟固化骨水泥的热暴露对大多数抗生素的稳定性影响最小，除庆大霉素外，通过免疫测定法测得其降解约25%。发现β-内酰胺类抗生素在37°C时降解相当迅速，无论是否有初始热暴露。在两种条件下，氨基糖苷类、糖肽类、四环素类和喹诺酮类均表现出优异的长期稳定性。
本研究为考虑局部应用抗生素的骨科医生以及希望开发下一代控释或缓释抗生素载体的材料科学家提供了有价值的数据集。E. 萨马拉、T. F. 莫里亚蒂、L. A. 德科斯特德、R. G. 理查兹、E. 高蒂尔、P. 瓦尔。模拟骨水泥固化的热处理条件下，抗生素在体温的水溶液中六周的稳定性。2017年；6:296 - 306。DOI: 10.1302/2046 - 3758.65.BJR - 2017 - 0276.R1
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