Clinic of Dermatology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche-Ospedali Riuniti, Ancona 60020, Italy.
Int J Mol Sci. 2013 Aug 7;14(8):16321-32. doi: 10.3390/ijms140816321.
We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.
我们研究了替加环素和 FS8 单独或联合应用在预防葡萄球菌血管移植物感染大鼠模型假体生物膜中的疗效。通过将 Dacron 移植物植入成年雄性 Wistar 大鼠背部皮下组织，然后用 2 x 107 个金黄色葡萄球菌（Smith 扩散株）的菌落形成单位进行局部接种，建立移植物感染。研究包括对照组、未接受任何抗生素预防的污染组以及接受以下治疗的三个污染组：（i）腹腔内替加环素，（ii）FS8 浸泡移植物，和（iii）替加环素加 FS8 浸泡移植物，每组包括 15 只动物。通过超声处理和定量琼脂培养评估感染负担。此外，进行了体外结合研究以量化 FS8 涂覆在假体表面的量。在体外研究中，替加环素与 FS8 联合使用时，与单独使用替加环素相比，对粘附细菌的 MIC（2.00 mg/L）和 MBC（4.00 mg/L）降低了四倍。用替加环素治疗的大鼠组显示出最低的细菌数量（4.4 x 104 ± 1.2 x 104 CFU/mL）。FS8 治疗组与对照组相比具有良好的活性，细菌数量为 6.8 x 104 ± 2.0 x 104 CFU/mL，差异有统计学意义。与单独使用细菌治疗的大鼠相比，联合使用 FS8 和替加环素治疗的大鼠观察到更强的细菌生长抑制作用，细菌数量为 101 CFU/mL 移植物。总之，FS8 具有影响生物膜形成的能力，并且是抗生素增强剂，提示 FS8 可作为替代或附加剂与常规抗菌药物联合使用，以预防葡萄球菌生物膜相关感染。
