PDF(Pubmed)
Abstract：
Methicillin-resistant Staphylococcus aureus (M RSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhance the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with similar potency between tested formulations. In MRSA-C1, minimal inhibitory concentrations (MIC) for Free RFB and liposomal RFB were 0.009 and 0.013 μg/mL, respectively. Minimum biofilm inhibitory concentrations able to inhibit 50% biofilm growth (MBIC50) for Free RFB and liposomal RFB against MRSA-C1 were 0.012 and 0.008 μg/mL, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. The in vivo results demonstrated a significant reduction in bacterial burden and growth index in major organs of mice treated with RFB formulations, as compared to Control and VCM (positive control) groups. Furthermore, the VCM therapeutic dose was two fold higher than the one used for RFB formulations, reinforcing the therapeutic potency of the proposed strategy. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.
摘要：
耐甲氧西林金黄色葡萄球菌（MRSA）感染，特别是生物膜组织的细菌，仍然是临床挑战和严重的健康问题。利福布汀(RFB),利福霉素类的抗生素,在以前的工作中显示出优异的抗葡萄球菌活性。这里,我们建议将RFB加载到脂质体中,旨在促进RFB在感染部位的积累,从而增强治疗效力。两株临床分离的MRSA,MRSA-C1和MRSA-C2用于测试开发的制剂，以及阳性对照，万古霉素（VCM）。游离和脂质体形式的RFB显示出高抗菌活性，在测试的制剂之间具有相似的效力。在MRSA-C1中，游离RFB和脂质体RFB的最小抑制浓度（MIC）为0.009和0.013μg/mL，分别。能够抑制游离RFB和脂质体RFB对MRSA-C1的50％生物膜生长（MBIC50）的最小生物膜抑制浓度为0.012和0.008μg/mL，分别。共聚焦显微镜研究证明了未负载和RFB负载的脂质体在细菌生物膜基质中的快速内化。在系统性MRSA-C1感染的小鼠模型中，Balb/c小鼠用20和40mg/kg体重的RFB制剂和VCM处理,分别。体内结果表明，用RFB制剂治疗的小鼠主要器官的细菌负荷和生长指数显着降低。与对照组和VCM(阳性对照)组相比。此外，VCM治疗剂量比用于RFB制剂的剂量高两倍，加强拟议策略的治疗效力。此外,RFB制剂是唯一与100%存活相关的制剂。全球范围内,这项研究强调了RFB纳米制剂作为对抗MRSA感染的有效和安全方法的潜力.
