Preventing Burn Wound Infection Using a Novel Free Radical Sterilization System

描述（由申请人提供）：仅在美国，每年就有大约200万例烧伤病例需要医疗护理，其中2万例需要进入专门的烧伤中心。烧伤患者发病和死亡的主要原因之一是感染。事实上，对于那些烧伤面积大于体表总面积40%的患者，75%的死亡是由于感染。因此，实施有效的感染预防策略和避免耐药微生物在患者之间传播是治疗烧伤患者的关键障碍。避免烧伤患者全身感染的一个基本要素在于预防烧伤创面本身的感染。不幸的是，烧伤创面是所有类型微生物生长的有吸引力的媒介，因为覆盖皮肤的损失创造了一个湿润的、富含蛋白质的、无血管的环境，有利于微生物的生长。目前，预防烧伤创面感染的标准护理策略包括使用局部抗菌剂，但这些局部抗菌剂并不能100%杀死微生物，并对烧伤患者产生各种不良影响。SuperPulse等离子体处理技术（SuperPulse PPT）开发了全新的非热等离子体自由基灭菌系统，是预防烧伤伤口感染的局部抗菌剂的无副作用替代品。SuperPulse PPT目前的灭菌装置背后的机制是产生一种非热等离子体/自由基流出物，可以安全地输送到感染的烧伤处。通过初步研究，SuperPulse PPT已经证明了这种自由基杀菌系统在体外杀死营养、孢子和生物膜形式的微生物的能力。此外，体内试验表明，这种灭菌系统可以杀死哺乳动物皮肤上的微生物，同时不伤害皮肤本身。因此，该装置有可能改变目前预防烧伤伤口感染的治疗模式，使其成为一种低成本、无副作用、对所有微生物都有效的系统。该研究将使用已建立的猪深部皮肤部分厚度烧伤模型，以金黄色葡萄球菌和铜绿假单胞菌这两种引起人类烧伤创面感染的常见生物创建多微生物烧伤创面感染。我们提出这一建议的主要目的是证明SuperPulse PPT自由基系统在预防烧伤创面感染方面与“金标准”外用抗菌药物Silvadene同样有效。如果我们的假设是正确的，SuperPulse PPT自由基灭菌系统有可能改变目前预防烧伤创面感染的治疗模式，成为一种高效、无副作用的方法，将显著减少烧伤创面感染及其由此产生的发病率和死亡率。

DESCRIPTION (provided by applicant): Approximately two million burn injury cases require medical attention on a yearly basis in the United States alone, with 20,000 of these cases requiring admission to specialized burn centers. One of the foremost causes of morbidity and mortality in the burn patient is infection. Indeed, for those patients with burn size greater than 40% of total body surface area, 75% of all deaths are due to infection. Thus, implementing effective strategies for infection prevention and avoiding transmission of resistant microorganisms from patient to patient is a critical barrier in the treatment of burn patients. A foundational element of avoiding systemic infection in the burn patient lies with preventing infection of the burn wound itself. Unfortunately, the burn wound is an attractive media for the growth of all types of microorganisms as loss of overlying skin creates a moist, protein-rich, avascular environment that facilitates microbiotic growth. Current, standard-of-care strategies for the prevention of burn wound infection involve the use of topical antimicrobials, but these topical agents do no kill 100% of microorganisms and display a variety of untoward effects in burn patients. SuperPulse Plasma Processing Technology (SuperPulse PPT) has developed totally novel, non-thermal plasma delivered free radical sterilization system that is a side effect-free alternative to topical antimicrobials for the prevention of burn wound infection. The mechanism behind SuperPulse PPT's current sterilization device involves generating a non-thermal plasma/free radical effluent that can safely be delivered to infected burn injuries. Through preliminary studies, SuperPulse PPT has demonstrated the ability of this free radical sterilization system to kill microorganisms in vegetative, spore, and biofilm forms in vitro. Additionally, in vivo testing has demonstrated that this sterilization system can kill microorganisms on mammalian skin while leaving the skin itself unharmed. Thus, this device has the potential to change the current treatment paradigm of preventing burn wound infections to a low cost, side effect-free system that is efficacious against all microorganisms. The proposed study will use an established porcine model of deep dermal partial thickness burn injury to create a polymicrobial burn wound infection with Staphylococcus aureus and Pseudomonas aeruginosa, two of the common organisms causing burn wound infection in humans. Our main objective with this proposal is to demonstrate that the SuperPulse PPT free radical system is equally efficacious at preventing burn wound infection in this model as the "gold standard" topical antimicrobial Silvadene. If our hypothesis is correct, the SuperPulse PPT free radical sterilization system has the potential to change the current treatment paradigm for prevention of burn wound infection to a highly efficacious, side effect-free method that will dramatically reduce burn wound infection and its resultant morbidity and mortality. PUBLIC HEALTH RELEVANCE: Burn wound infection remains an important source of morbidity, mortality, and health care cost. Standard-of-care measures for preventing burn wound infection rely heavily on the use of topical antimicrobials, but these agents are not 100% effective and have multiple negative side effects, which has fueled the search for more efficacious methods of burn wound sterilization. SuperPulse Plasma Processing Technology has developed a totally novel free radical sterilization system by combining non-thermal plasma processing with hydrogen peroxide and ozone technologies. This unique sterilization system has the potential to change the current treatment paradigm of preventing burn wound infections to a low cost, side effect-free system that is efficacious against even the most resistant microorganisms.