Wound Decontamination for the Prevention and Treatment of Multi-drug Resistant Ba

描述（由申请人提供）：多重耐药感染的频率正在以惊人的速度增加。同样令人关切的是，可用于有效治疗的治疗选择有限，导致与这些高耐药性感染相关的发病率和死亡率增加。通常，多重耐药感染表现为由耐甲氧西林金黄色葡萄球菌（MRSA）和其他多重耐药细菌引起的软组织或伤口感染。拟议项目的重点是开发一种无毒的局部冲洗产品。这种伤口去污剂能够帮助从伤口清除细菌，杀死广谱的耐药和非耐药细菌，并提供防止细菌定植的残留预防效果。通过聚集细菌，感染性病原体更容易从伤口冲洗。任何未被去除的细菌被聚合物衍生物杀死，残留的材料防止细菌定植。这项拟议的工作优化了所需的浓度和分子的特定分子量配方，以促进伤口清洁和保护免受随后的感染。这些研究将导致II期体内研究，以支持所需的监管申请。目的是提供一种新型、高效和高度生物相容性的治疗方法，用于治疗和预防伤口感染，特别是解决多重耐药细菌。 公共卫生相关性：一种天然抗菌聚合物衍生物已被开发出来，它对多重耐药菌和非耐药菌具有广谱抗菌活性。该聚合物是一种生物相容的无毒多糖，不被身体吸收或代谢，是局部应用的理想选择。此外，由于分子与细菌的作用机制是物理膜损伤，因此聚合物不太可能引起抗生素耐药性。我们的目标集中在表征和开发一种无毒、有效的伤口去污冲洗液，用于预防和治疗多药耐药伤口感染。预期优化的制剂有助于通过结块去除致病菌，降低剩余细菌的活力，并为细菌定植提供有限的残留屏障。这项拟议的研究旨在了解和优化与结块、粘附和残留效应相关的分子变量，并最终提供一种新型治疗产品，以预防和治疗多药耐药伤口感染。

DESCRIPTION (provided by applicant): The frequency of multi-drug resistant infections is increasing at an alarming rate. Equally concerning is the limited therapeutic options available for effective treatment, resulting in increased morbidity and mortality associated with these highly resistant infections. Frequently, multi-drug resistant infections manifest as soft tissue or wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other multi-drug resistant bacteria. The proposed project focuses on the development of a non-toxic, topical rinse product. This wound decontaminant is capable of helping to clear bacteria from wound, killing a broad spectrum of resistant and non-resistant bacteria, and providing a residual prophylactic effect that prevents bacterial colonization. By aggregating bacteria, the infectious pathogens are more easily rinsed from the wound. Any bacteria not removed are killed by the polymer derivative and residual material prevents bacterial colonization. This proposed work optimizes the concentration required and specific molecular weight formulation of the molecule to facilitate wound cleaning and protection from subsequent infection. These studies will lead to in vivo studies in Phase II in support of required regulatory applications. The goal is to provide a novel, highly effective and highly biocompatible therapy for the treatment and prevention of wound infections, particularly addressing bacteria that are multi-drug resistant. PUBLIC HEALTH RELEVANCE: A natural antimicrobial polymer derivative has been developed that demonstrates broad-spectrum antibacterial activity against multi-drug resistant and non-resistant bacteria. The polymer is a biocompatible, non-toxic polysaccharide, is not absorbed or metabolized by the body, and is ideal for topical applications. Further, because the mechanism of action of the molecule with bacteria is physical membrane damage, the polymer is less likely to evoke antibiotic resistance. Our aims focus on the characterization and development of a non-toxic, efficacious wound decontamination rinse for prevention and treatment of multi-drug resistant wound infections. The optimized formulation is expected to facilitate the removal of pathogenic bacteria via clumping, reducing the viability of remaining bacteria and providing a limited residual barrier to bacterial colonization. This proposed research is intended to understand and optimize the molecular variables associated with clumping, bactericide and residual effect and ultimately provide a novel therapeutic product to prevent and treat multi-drug resistant wound infections.