Laycock Phillip A, Cooper John J, Howlin Robert P, Delury Craig, Aiken Sean, Stoodley Paul
Biocomposites Ltd., Keele Science Park, Keele, Staffordshire ST5 5NL, UK.
National Institute for Health Research Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University of Southampton NHS Foundation Trust, Southampton SO17 1BJ, UK.
Materials (Basel). 2018 Nov 13;11(11):2265. doi: 10.3390/ma11112265.
15 different antibiotics were individually mixed with commercially available calcium sulfate bone void filler beads. The antibiotics were: amikacin, ceftriaxone, cefuroxime, ciprofloxacin, clindamycin, colistamethate sodium, daptomycin, gentamicin, imipenem/cilastatin, meropenem, nafcillin, rifampicin, teicoplanin, tobramycin and vancomycin. The efficacy of specific released antibiotics was validated by zone of inhibition (ZOI) testing using a modified Kirby⁻Bauer disk diffusion method against common periprosthetic joint infection pathogens. With a subset of experiments (daptomycin, rifampin, vancomycin alone and rifampin and vancomycin in combination), we investigated how release varied over 15 days using a repeated ZOI assay. We also tested the ability of these beads to kill biofilms formed by 35984, a prolific biofilm former. The results suggested that certain antibiotics could be combined and released from calcium sulfate with retained antibacterial efficacy. The daptomycin and rifampin plus vancomycin beads showed antimicrobial efficacy for the full 15 days of testing and vancomycin in combination with rifampin prevented resistant mutants. In the biofilm killing assay, all of the antibiotic combinations showed a significant reduction in biofilm bacteria after 24 h. The exposure time was an important factor in the amount of killing, and varied among the antibiotics.
将15种不同的抗生素分别与市售硫酸钙骨缺损填充珠混合。这些抗生素分别是：阿米卡星、头孢曲松、头孢呋辛、环丙沙星、克林霉素、黏菌素甲磺酸钠、达托霉素、庆大霉素、亚胺培南/西司他丁、美罗培南、萘夫西林、利福平、替考拉宁、妥布霉素和万古霉素。使用改良的Kirby⁻Bauer纸片扩散法，通过抑菌圈（ZOI）测试，针对常见的假体周围关节感染病原体，验证特定释放抗生素的疗效。在一组实验中（单独使用达托霉素、利福平、万古霉素以及利福平和万古霉素联合使用），我们使用重复的抑菌圈检测法，研究了15天内释放情况的变化。我们还测试了这些珠子杀死由35984形成的生物膜的能力，35984是一种大量形成生物膜的菌株。结果表明，某些抗生素可以与硫酸钙结合并释放，同时保持抗菌效果。达托霉素、利福平加万古霉素的珠子在整个15天的测试中均显示出抗菌效果，万古霉素与利福平联合使用可防止耐药突变体产生。在生物膜杀灭试验中，所有抗生素组合在24小时后生物膜细菌数量均显著减少。暴露时间是杀灭量的一个重要因素，不同抗生素之间存在差异。
