Biofilm Infections in Postsurgical, Trauma, and Critically Ill Patients

术后、创伤和危重患者的生物膜感染

• 批准号: 8400893
• 负责人: Carol L Wells
• 金额: $ 29.14万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8400893
• 关键词: Adherence; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Attention; Awareness; Bacteria; Biochemical; Biological Preservation; Biomass; Blood Platelets; Blood Vessels; Burn injury; Catheters; Cause of Death; Cell Separation; Cells; Chronic; Clinical; Clinical Medicine; Communicable Diseases; Communities; Complex; Confocal Microscopy; Critical Illness; DNA; Data; Development; Devices; Disease; Dyes; Electron Microscopy; Elements; Endocarditis; Enterococcus; Enterococcus faecalis; Equipment; Erythrocytes; Event; Excision; Family suidae; Fixatives; Fluorescent in Situ Hybridization; Genus staphylococcus; Glycolipids; Glycoproteins; Growth; Heart Valves; In Vitro; Incubated; Indium; Infection; Infection prevention; Laboratories; Lead; Leukocytes; Life; Location; Manuscripts; Methodology; Methods; Microbe; Microbial Biofilms; Morbidity - disease rate; Morphologic artifacts; Nosocomial Infections; Operative Surgical Procedures; Patients; Physiology; Play; Pneumonia; Polysaccharides; Population; Predisposition; Proteins; Publishing; Research Personnel; Resolution; Risk; Role; Scanning Electron Microscopy; Sepsis; Series; Silastic; Site; Staphylococcus aureus; Structure; Surface; Surgical sutures; Testing; Time; Trauma; Venous; Work; Wound Infection; antimicrobial drug; attributable mortality; base; catheter related infection; cost; design; extracellular; implantable device; in vivo; mortality; novel; public health relevance; research study; therapy development

DESCRIPTION (provided by applicant): A biofilm is a population of bacteria growing on a surface and surrounded by a complex extracellular polymeric substance composed of proteins, glycoproteins, glycolipids, polysaccharides, and DNA. There is increasing awareness that biofilms are involved in the majority of infectious diseases, especially those in postsurgical, trauma, and critically ill patients. These diseases include pneumonia in ventilated patients, endocarditis, burn wound infections, and infections of indwelling devices. Postsurgical, trauma, and critically ill patients are at increased risk for catheter-related infections and surgical site infections. Nosocomial infections are among the ten leading causes of death in the USA, and more than 20% of nosocomial infections are surgical site infections and a large proportion of these involve surgical suture. Vascular catheters are the most common cause of bloodstream infections and it is estimated that 250,000 catheter-associated bloodstream infections occur annually with high attributable mortality (12 to 25%) and annual costs ranging from $300 million to several billion dollars. This proposal focuses on two of the most prevalent etiologic agents of catheter-related and surgical site infections, namely Staphylococcus aureus and Enterococcus faecalis. Not only are these bacteria prevalent in biofilm-related infections, the antimicrobial resistance associated with staphylococci and enterococci continues to increase making it increasingly important to discover new strategies to prevent these infections. The force behind this proposal is our recent discovery of unusual (heretofore unrecognized), large cellular elements that appear early in biofilm formation (within 15 min) and are likely of critical importance. We have compelling preliminary evidence that these large cellular elements may not only play a pivotal role in initial attachment of the biofilm to the substratum (the surface) and may thus represent a common on-off switch in biofilm initiation, but these relatively large cells may be the putative persister cells thought to be primarily responsible for the increased antibiotic resistance of the biofilm. We have four specific aims. Aim 1 will characterize the large, newly discovered cellular elements that appear early in biofilm development. Aim 2 will compare the development and composition of S. aureus and E. faecalis biofilms cultivated in vitro on suture and on silastic catheter material, focusing on early developments. Aim 3 will clarify the role of the large, newly discovered cellular elements in initial biofilm development and in antibiotic susceptibility. Aim 4 will characterize the vegetations within discarded in vivo vascular catheters removed from postsurgical, trauma, and critically ill patients, and compare these data with biofilm vegetations cultivated in vitro. Experimental methods include standard microbiological methods, confocal microscopy and high resolution electron microscopy, cell sorting, fluorescence in situ hybridization, and biochemical analyses. Resulting data will significantly contribute to our understanding of the initiation and treatment of biofilm infections, especially those associated with postsurgical, trauma, and critically ill patients.

描述（由申请人提供）：生物膜是生长在表面并被由蛋白质、糖蛋白、糖脂、多糖和DNA组成的复杂细胞外聚合物质包围的细菌群。越来越多的人认识到生物膜与大多数传染病有关，特别是在术后、创伤和危重病人中。这些疾病包括通气患者的肺炎、心内膜炎、烧伤创面感染和留置器感染。术后、创伤和危重患者发生导管相关感染和手术部位感染的风险增加。医院感染是美国十大死亡原因之一，超过20%的医院感染是手术部位感染，其中很大一部分涉及手术缝合。血管导管是血流感染的最常见原因，据估计，每年发生25万例导管相关血流感染，可归因死亡率高（12%至25%），每年的费用从3亿美元到数十亿美元不等。本建议着重于导管相关和手术部位感染的两种最常见的病因，即金黄色葡萄球菌和粪肠球菌。这些细菌不仅在生物膜相关感染中普遍存在，而且与葡萄球菌和肠球菌相关的抗菌素耐药性也在不断增加，这使得发现预防这些感染的新策略变得越来越重要。这一建议背后的力量是我们最近发现的不寻常的（迄今为止未被认识到的），在生物膜形成的早期（在15分钟内）出现的大细胞元件，可能是至关重要的。我们有令人信服的初步证据表明，这些较大的细胞元件可能不仅在生物膜与基质（表面）的初始附着中起关键作用，因此可能代表生物膜起始的常见开关，而且这些相对较大的细胞可能是假定的持久性细胞，被认为是生物膜增加抗生素耐药性的主要原因。我们有四个具体目标。目的1将描述在生物膜发育早期出现的大的、新发现的细胞元件。目的2将比较体外培养的金黄色葡萄球菌和粪球菌生物膜在缝线和硅橡胶导管材料上的发育和组成，重点关注早期的发展。目的3将阐明大的，新发现的细胞元件在初始生物膜发育和抗生素敏感性中的作用。目的4将描述从术后、创伤和危重患者中取出的废弃体内血管导管内的植被，并将这些数据与体外培养的生物膜植被进行比较。实验方法包括标准微生物学方法、共聚焦显微镜和高分辨率电子显微镜、细胞分选、荧光原位杂交和生化分析。所得数据将显著有助于我们理解生物膜感染的开始和治疗，特别是那些与术后、创伤和危重患者相关的感染。