Department of Biomedical Engineering, University of Memphis, 328A Engineering Technology Building, Memphis, TN, 38152, USA,
Clin Orthop Relat Res. 2013 Oct;471(10):3158-64. doi: 10.1007/s11999-013-2988-5. Epub 2013 Apr 20.
Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment.
QUESTIONS/PURPOSES: In this pilot study, we asked whether antiseptic and antibiotic combinations provided in vitro synergism against Staphylococcus aureus, whether synergism reduces cell viability, and whether their combination releases drugs at inhibitory levels.
To investigate the pharmacodynamics among three combinations of the antiseptic chlorhexidine digluconate (CHX) with the antibiotics amikacin, daptomycin, and vancomycin (VAN) (n=1), we determined the fractional inhibitory concentration (FIC) index against S aureus Cowan I. The determined synergistic combination of CHX and VAN was evaluated for cell compatibility using NIH/3T3 fibroblasts (n=3) and the drug release profile from a chitosan sponge device (n=5).
With an FIC index<0.5, the combination of CHX+VAN exhibited synergism against S aureus. CHX concentrations≥3.91 μg/mL resulted in fibroblast viability decrease, whereas the combination of CHX+VAN did not decrease fibroblast viability until their concentrations reached ≥7.81 μg/mL. The CHX and VAN release profile, both individually and in combination, was an initial bolus with no difference between eluate concentrations after Day 5.
CHX+VAN combination may be delivered locally by a chitosan sponge that synergistically inhibits S aureus growth.
The use of synergism between combined antibiotic and antiseptics delivered at high local concentrations with an implanted chitosan sponge may provide a useful alternative infection treatment option.
尽管细菌对抗生素的耐药性在不断增加，但用于补偿的新抗生素却越来越少。局部输送具有协同作用的防腐剂和抗生素的壳聚糖海绵装置可能提供了一种替代感染治疗的方法。
问题/目的：在这项初步研究中，我们询问了防腐剂洗必泰（CHX）与抗生素阿米卡星、达托霉素和万古霉素（VAN）联合使用是否具有协同作用，是否降低细胞活力，以及它们的组合是否以抑制水平释放药物。
为了研究三种防腐剂洗必泰（CHX）与抗生素阿米卡星、达托霉素和万古霉素（VAN）联合使用的协同作用，我们测定了对金黄色葡萄球菌 Cowan I 的分数抑菌浓度（FIC）指数。用 NIH/3T3 成纤维细胞（n=3）评估确定的 CHX 和 VAN 协同组合的细胞相容性，并使用壳聚糖海绵装置（n=5）评估药物释放情况。
FIC 指数<0.5 时，CHX+VAN 联合使用对金黄色葡萄球菌表现出协同作用。CHX 浓度≥3.91μg/ml 会导致成纤维细胞活力下降，而 CHX+VAN 联合使用直到其浓度达到≥7.81μg/ml 才会降低成纤维细胞活力。CHX 和 VAN 的释放曲线，无论是单独还是联合使用，均表现为初始突释，第 5 天后洗脱液浓度无差异。
CHX+VAN 联合可以通过壳聚糖海绵局部给药，协同抑制金黄色葡萄球菌生长。
用高浓度局部输送的联合抗生素和防腐剂的协同作用，结合植入的壳聚糖海绵，可能为感染治疗提供一种有用的替代选择。
