Preventing Burn Wound Infection Using a Novel Free Radical Sterilization System

描述（由申请人提供）：仅在美国，每年约有200万例烧伤病例需要医疗护理，其中20，000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全身表面积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的传播是烧伤患者治疗中的关键障碍。避免烧伤患者全身感染的基本要素在于防止烧伤伤口本身的感染。不幸的是，烧伤伤口是所有类型的微生物生长的有吸引力的介质，因为失去覆盖的皮肤会产生有利于微生物生长的潮湿、富含蛋白质、无血管的环境。目前，用于预防烧伤伤口感染的标准护理策略涉及使用局部抗菌剂，但这些局部药剂不能100%杀死微生物，并且在烧伤患者中显示出各种不良反应。SuperPulse等离子体处理技术（SuperPulse PPT）开发了全新的非热等离子体传递自由基灭菌系统，该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目前的灭菌设备背后的机制包括产生一种非热等离子体/自由基流出物，可以安全地输送到受感染的烧伤。通过初步研究，SuperPulse PPT已经证明了这种自由基灭菌系统在体外杀死营养体、孢子和生物膜形式的微生物的能力。此外，体内测试已经证明，这种灭菌系统可以杀死哺乳动物皮肤上的微生物，同时使皮肤本身不受伤害。因此，该装置有可能将当前预防烧伤伤口感染的治疗范例改变为对所有微生物有效的低成本、无副作用的系统。拟定研究将使用已建立的深真皮部分厚度烧伤猪模型，以产生金黄色葡萄球菌和铜绿假单胞菌（两种常见的导致人类烧伤伤口感染的微生物）的多微生物烧伤伤口感染。我们的主要目的是证明SuperPulse PPT自由基系统在该模型中预防烧伤伤口感染与“金标准”局部抗菌剂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伤口感染的治疗模式，成为一种高效、无副作用的方法，将大大减少烧伤伤口感染及其导致的发病率和死亡率。 公共卫生相关性：烧伤伤口感染仍然是发病率、死亡率和医疗保健费用的重要来源。用于预防烧伤伤口感染的标准护理措施严重依赖于局部抗菌剂的使用，但这些药剂不是100%有效的，并且具有多种负面副作用，这促使人们寻找更有效的烧伤伤口灭菌方法。SuperPulse等离子体处理技术通过将非热等离子体处理与过氧化氢和臭氧技术相结合，开发了一种全新的自由基灭菌系统。这种独特的灭菌系统有可能改变目前预防烧伤伤口感染的治疗模式，成为一种低成本、无副作用的系统，即使对最耐药的微生物也有效。

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.