Innovative technologies to effectively treat Multi-drug resistant and/or biofilm-

描述（由申请人提供）：本I期项目旨在评价一系列预防和治疗伤口感染的新型药物组合。伤口具有促进感染发展的某些特征：存在失活组织、异物、凝块、积液以及伤口被来自伤员皮肤、环境和医院的细菌污染。来自伊拉克和阿富汗军事行动的医学报告证实了多重耐药细菌（MDR）的出现，如鲍曼不动杆菌、肺炎克雷伯菌、耐甲氧西林金黄色葡萄球菌和多重耐药铜绿假单胞菌。由这些多重耐药生物体引起的感染似乎导致显著的发病率和死亡率。生物膜内的细菌固有地对防腐剂、杀微生物剂和宿主免疫系统不敏感。使问题进一步复杂化的是，MDR细菌可以在伤口部位或植入物表面形成生物膜，引起对宿主免疫系统和抗生素治疗不敏感的感染。一个有效的抗菌策略，以防止和治疗生物膜是迫切需要在军事和民用护理。在这个项目中，我们提出了一系列新的药物组合作为薄膜制剂。将在伤口敷料模型中使用纳米原纤壳聚糖网作为局部递送载体来评估涂膜制剂的功效。所提出的技术结合了包括纳米纤维屏障、止血活性、止血膜功效和控释策略在内的特征。 公共卫生相关性：据估计，在美国，医院感染每年影响约200万人，并且医疗保健提供者花费超过110 B美元。伤口护理和留置导管是两个最常见的相关感染领域，在20世纪90年代经历了抗菌器械的激增。到2007年，美国伤口护理市场已增长到约100 B。这种增长推动了减少感染的努力，从而导致抗菌敷料的发展。

DESCRIPTION (provided by applicant): This Phase I project is to evaluate a series of novel drug combinations to prevent and treat wound infections. Wounds have certain characteristics that promote the development of infections: the presence of devitalized tissue, foreign bodies, clots, fluid collections, and contamination of wounds with bacteria from the casualty's skin, the environment and the hospital. Medical reports from the military actions in Iraq and Afghanistan confirmed the emergence of multi-drug resistant bacteria (MDR) such as Acinetobacter baumannii, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and multi-drug resistant Pseudomonas aeruginosa. Infections caused by these multi-drug resistant organisms appear to result in significant morbidity and mortality. Bacteria within biofilms are inherently insensitive to antiseptics, microbicides, and host immune system. To complicate the problem further, the MDR bacteria can form biofilm at the wound sites or implant surfaces, causing infections that are insensitive to host immune system and antibiotic therapies. An effective antimicrobial strategy to prevent and treat biofilm is desperately needed in both military and civilian care. In this project, we propose a series of novel drug combinations as antibiofilm formulations. Efficacy of the antibiofilm formulations will be assessed in a wound dressing model using nanofibrillar chitosan meshes as a topical delivery carrier. The proposed technology combines characteristics including nanofibrillar barrier, hemostatic activity, antibiofilm efficacy, and controlled release strategy. PUBLIC HEALTH RELEVANCE: It was estimated that nosocomial infections affect about 2.0 M people in the U.S. each year and costs more than $11.0 B to the healthcare providers. Wound care and indwelling catheters, the two most commonly associated areas of infection, experienced a surge of antimicrobial devices in the 1990s. By 2007, the US wound care market has grown to an estimated $10 B. This growth has driven efforts to reduce infection that resulted in the development of antimicrobial dressings.