金黄色葡萄球菌性创伤性骨髓炎术后高效抗体配伍被动免疫治疗的机理研究

The genes mutation in Staphylococcus aureus (S. aureus) is the key reason of developing antimicrobial resistant. There is no an effective solution for S.aureus infected osteomyelitis yet. Based on our previous study results by leading AO clinical priority program (AOCPP) in China and found： 1) It’s significantly regional characteristics of bacteria infections and antibiotic resistance in postoperative traumatic limb fractures. The most common infections were monomicrobial in the lower extremities and forearm. S. aureus was the most common pathogen, which was present in 60.78% cases, and 40.74% were caused by MRSA. These findings support an empiric antibiotic therapy of a carbapenum and vancomycin, for postoperative infections in patients with traumatic limb fractures. 2) The microbial film formation and bacterial colonization within of cortical bone microcrack are the cause of infection recurrence. 3) Based on genes and multivalent antigen screening techniques, we found that the antibodies of IsdB、1C11 are potential ideally candidates that had significantly therapeutic efficacy. However, the microbial couldn’t be able to completely eliminate by each single antibody, which was indicating the limitation of single antibody therapy.Meanwhile, the majority microbial strains of infection in China are ST239, ST5 and ST2582 etc. Their specific antigens have shown different characteristics along with the time by. Thus, our research goals of this proposal are 1) based on AOCPP,we have collected bone infection specimen in China and are investigating 14 different antigens of S.aureus to discover their antigen characters. 2) To determine the efficacy of multiple antibodies combination in vivo by using a well established murine tibiae infection model. 3) To evaluate the value of the image of MRI and CT on early bone infection vs. their serum biomarkers. All above aims are to establish clinical useful specific markers for evidence-based diagnosis and.therapy for osteomyelitis.

金黄色葡萄球菌（S.aureus）感染性骨髓炎术后的治疗尚无满意疗效，与其感染菌株的耐药基因变异密切相关。申请者研究组参与AOCPP骨感染的研究结果表明: S.aureus的耐药谱有显著的地域性特征；细菌生物膜的形成、细菌定植于创面密质骨微裂内是术后复发的根源；基于基因和多抗原筛选发现IsdB、1C11等抗体有明显治疗效果、但不能完全清除病菌，提示免疫治疗策略仍需探讨。国内感染以ST239、ST5、ST2582等菌株为主，其特异抗原可能有时段性差异。因此本研究目的是1）基于AOCPP骨感染患者注册系统收集的国内临床标本、利用高通量Bioluminex明确14种S.aureus相关抗原在不同时段的表达水平；2）构建小鼠胫骨感染模型、明确高效价多抗体配伍对残余定植细菌的清除作用；3）探讨影像及血清学标志物对早期感染复发的特征及其意义。旨在为骨髓炎术后个体化治疗提供精准的循证医学证据。

金黄色葡萄球菌（S.aureus）感染性骨髓炎术后的治疗尚无满意疗效，与其感染菌株的耐药基因变异密切相关。申请者研究组参与AOCPP骨感染的研究结果表明： S.aureus的耐药谱有显著的地域性特征；细菌生物膜的形成、细菌定植于创面密质骨微裂内是术后复发的根源；基于基因和多抗原筛选发现IsdB、1C11等抗体有明显治疗效果、但不能完全清除病菌，提示免疫治疗策略仍需探讨。国内感染以ST239、ST5、ST2582等菌株为主，其特异抗原可能有时段性差异。因此本研究目的是1）基于AOCPP骨感染患者注册系统收集的国内临床标本、利用高通量Bioluminex明确14种S.aureus相关抗原在不同时段的表达水平；2）构建小鼠胫骨感染模型、明确高效价多抗体配伍对残余定植细菌的清除作用；3）探讨影像及血清学标志物对早期感染复发的特征及其意义。旨在为骨髓炎术后个体化治疗提供精准的循证医学证据。

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