Delayed Onset of Biofilm Formation and CAUTI with Superhydrophobic Catheters

使用超疏水导管延迟生物膜形成和 CAUTI 的发生

• 批准号: 8251454
• 负责人: Sanjiv Lalwani
• 金额: $ 15万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251454
• 关键词: Delayed; Onset; Biofilm; Formation; CAUTI

DESCRIPTION (provided by applicant): Catheter-associated urinary tract infections (CAUTI) occur in >40& of the 21-50% patients that are administered indwelling catheters, annually costing a staggering $421-$451 million in medical intervention, antimicrobial treatments and frequent catheter replacements in the US alone. Increased patient trauma cannot be overlooked: when a CAUTI episode becomes symptomatic, the resulting sequelae can range from mild (fever, urethritis and cystitis) to severe (acute pyelonephritis, renal scarring, calculu formation and bacteremia). Organisms that lead to a CAUTI gain access in one of two ways: through the external lumen of the catheter or through the internal lumen. Attempts at mitigating CAUTIs, which have shown better efficacy extraluminally than intraluminally, have been directed at developing antimicrobial action on the catheter surface: (i) silver alloy urinary catheters are prone to antimicrobial resistance development; (ii) antimicrobial- impregnated catheters using several drugs/drug combinations elicit yet-to-be-established confidence in their efficacy. The root cause lies in the early onset of contamination where adhesion of bacteria to the catheter surface initiates a cascade of events (protein syntheses, etc.) leading to development of antibiotic resistance and the formation of thick biofilms. Two important consequences must be recognized: i) leaching of antibiotic- resistant bacterial into the bladder can cause serious infections, and; ii) attempts to control bacterial proliferation by means of antimicrobial action o the surface will constantly prove to be ineffective (as observed). With over 1 million cases of CAUTI reported in the United States annually, the claim that this is an area of high medical concern is not far-fetched. Therefore, the introduction of a new catheter technology with the potential to induce a sustainable paradigm shift that overcomes the limitations of the current state-of-the-art is warranted. This proposed Phase I SBIR effort is specifically designed to address the above challenge. In this effort, we propose a new superhydrophobic catheter technology. The prevalent hypothesis is that instead of moot attempts to control adhered, drug-resistant bacteria, catheters with super-hydrophobic internal surface should allow natural flow of urine to efficiently wash-off any adhered bacteria and exhibit minimal accommodation to new colonizing bacteria, thereby delaying bacterial proliferation, bio-film formation and subsequent complications. During this Phase I project, our overall goal is to demonstrate proof-of-concept delayed onset of bio-film formation by pursuing a series of specific aims, namely: (i) a uropathogen-inhospitable catheter internal lumen; (ii) optimized coating strength and stability, and; (iii) improved catheter functional lifetime Improved catheter functional lifetime. Successful completion of these specific aims should demonstrate ample feasibility of this catheter technology platform and should allow us to plan more comprehensive technology development and commercialization thrusts, in addition to exploration of other applied models in a follow-on Phase II effort. PUBLIC HEALTH RELEVANCE: We propose to generate and validate a catheter technology that exhibits prevention over cure: a coating formulation and mechanism that prevents adhesion of bacteria, which eventually develop antibiotic resistance and cause severe infections, to the catheter surface over state-of-the-art catheters with antimicrobial surfaces. Benefits derived should decrease healthcare costs, decrease infection and mortality rates and improve overall patient quality-of-life.

描述(由申请人提供)：导管相关性尿路感染(CAUTI)发生在21-50%的接受留置导尿管的患者中，每年仅在美国就花费了惊人的4.21-4.51亿美元用于医疗干预、抗菌治疗和频繁更换导尿管。患者创伤增加不容忽视：当CAUTI发作出现症状时，所产生的后遗症可能从轻微的(发烧、尿道炎和膀胱炎)到严重的(急性肾盂肾炎、肾脏疤痕、结石形成和菌血症)。导致CAUTI的生物体通过两种方式之一进入：通过导管的外腔或通过内腔。减轻导尿管感染的尝试是为了在导尿管表面发挥抗菌作用：(I)银合金导尿管容易产生抗菌力；(Ii)使用几种药物/药物组合的抗菌剂浸透导尿管使人们对其疗效产生信心，而铝外导尿管比铝内导尿管显示出更好的疗效。根本原因在于过早出现污染，细菌附着在导管表面引发了一系列事件(蛋白质合成等)。导致抗生素耐药性的发展和厚厚的生物膜的形成。必须认识到两个重要后果：i)耐抗生素细菌渗入膀胱可导致严重感染；ii)通过表面抗菌作用来控制细菌增殖的尝试将不断被证明是无效的(如观察到的)。由于美国每年报告的CAUTI病例超过100万例，认为这是一个高度医疗问题的地区的说法并不牵强。因此，引入一种新的导管技术，有可能导致可持续的范式转变，克服当前最先进技术的局限性，是有必要的。这项拟议的第一阶段SBIR工作是专门为应对上述挑战而设计的。为此，我们提出了一种新的超疏水导管技术。流行的假设是，与控制黏附的抗药性细菌的模拟尝试不同，具有超疏水内表面的导管应该允许尿液的自然流动有效地洗掉任何黏附的细菌，并对新的定植细菌表现出最小的适应能力，从而延缓细菌的增殖、生物膜的形成和随后的并发症。在此第一阶段项目中，我们的总体目标是通过追求一系列特定目标来证明概念验证延迟了生物膜的形成，即：(I)不适宜使用尿路病原体的导管内腔；(Ii)优化涂层强度和稳定性；以及(Iii)改善导管功能寿命。这些具体目标的成功完成将证明这一导管技术平台的充分可行性，并使我们能够规划更全面的技术开发和商业化推进，以及在后续的第二阶段工作中探索其他应用模型。 与公共健康相关：我们建议开发和验证一种预防重于治疗的导管技术：一种涂层配方和机制，可防止细菌在具有抗菌表面的最先进导管上与导管表面粘连，最终产生抗生素耐药性并导致严重感染。由此产生的好处应该会降低医疗成本，降低感染率和死亡率，并提高患者的整体生活质量。