Controlling Catheter-Associated Urinary Tract Infections Using Smart Catheters with Rationally Designed Active Topographies

使用具有合理设计的主动拓扑的智能导管控制导管相关的尿路感染

• 批准号: 10524038
• 负责人: Dacheng Ren
• 金额: $ 43.13万
• 依托单位: SYRACUSE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524038
• 关键词: Adhesions; Affect; Antibiotics; Antimicrobial Resistance; Bacteria; Biomass; Bladder; Bladder Control; Blinded; Blood coagulation; Catheterization; Catheters; Cells; Cellular Structures; Cessation of life; Copper; Development; Dose; Drainage procedure; Electromagnetic Fields; Engineering; Environment; Enzyme-Linked Immunosorbent Assay; Excision; Extracellular Matrix; Failure; Frequencies; Gender; Gene Expression Profiling; Goals; Growth; High Prevalence; Histologic; Hour; Immunity; In Vitro; Infection; Infection Control; Infection prevention; Infective cystitis; Inflammation; Kidney; Left; Long-Term Care; Magnetism; Medical; Methods; Microbe; Microbial Biofilms; Modeling; Molds; Morbidity - disease rate; Movement; Mucous Membrane; Mucous body substance; Multiple Bacterial Drug Resistance; Nosocomial Infections; Operative Surgical Procedures; Oryctolagus cuniculus; Patient Care; Patients; Pattern; Phagocytosis; Physiology; Play; Polymers; Predisposition; Prevalence; Prevention; Production; Proteus mirabilis; Public Health; Recovery; Research; Role; Route; Safety; Side; Surface; Technology; Testing; United States; Urease; Urethra; Urinary tract; Urine; Uropathogenic E. coli; Virulence Factors; active control; antimicrobial; antimicrobial drug; aqueous; catheter associated UTI; cell motility; cytokine; design; experimental study; fabrication; fluorescence imaging; healthcare-associated infections; in vivo; in vivo evaluation; lithography; mechanical properties; meter; microbial; mortality; multidrug tolerance; nanoparticle; novel; prevent; prototype; rational design; simulation; technology platform; urinary

Catheter associated urinary tract infection (CAUTI) is one of the most common healthcare-associated infections (HAIs), with a prevalence of 13 – 15% in the United States. CAUTIs are also blamed for increased morbidity and mortality of affected patients with an estimated 13,000 deaths annually. It is well known that the abiotic catheter materials are prone to colonization of microbes, which then ascend the catheter via motility and biofilm formation, causing infections in the urinary tract. Due to the protection of the biofilm matrix and slow growth of attached cells, biofilm cells are up to 1,000 times more resistant to antimicrobials than the planktonic cells of the same species. Thus, CAUTIs are difficult to treat and blockage of the catheter lumen can occur especially during long-term use, leading to stone formation and infections of the bladder and even kidney. Treatment of CAUTIs with high doses of antimicrobial agents can also adversely promote the development of multidrug resistant bacteria. Despite extensive research to date, no current technology can provide long-term (>30 days) fouling control. This unmet challenge motivated us to engineer smart catheters to ultimately eradicate CAUTI. Recently, the PI’s lab developed a new antifouling strategy based on active topography that drives magnetically responsive micron-size pillars to beat with a tunable frequency and force level. This was achieved by loading Fe3O4 nanoparticles on the tip of each pillar and generating an electromagnetic field using an insulated copper coil embedded in the catheter wall (thus does not change the catheter profile). This novel design demonstrated unprecedented strong antifouling activities that can inhibit biofilm formation of multiple species by up to 3.6 logs (99.98%) for 48 hours and remove mature biofilms by up to 3.5 logs (99.97%) on demand with a stronger force, compared to the flat control. A prototype catheter with micron-size pillars on the inner wall was engineered and remained clean for more than 30 days under the flow of artificial urine and the challenge of uropathogenic Escherichia coli (UPEC), while both flat and static controls were completely blocked by UPEC biofilms within 5 days. These results motivated the team to further develop this technology to also control biofouling of the outer catheter wall, which is covered by urethral mucosa and involved in two thirds of CAUTIs. Integrated simulation and experimental studies will be conducted to understand the mechanism of biofouling control by active topography and the design principles for antifouling topographies on both sides of the catheter wall. The best design will be further tested in vivo using a rabbit model of CAUTI induced by UPEC. Both CAUTI prevention (up to 30 days) and removal of established biofilms will be evaluated.

导管相关的尿路感染（CAUTI）是最常见的医疗保健之一 感染（HAI），美国的患病率为13％至15％。凯蒂（Cautis）也被指责为 估计每年13,000例死亡的患者的发病率和死亡率增加。这是 众所周知，非生物导管材料易于定植微生物，然后上升 通过运动和生物膜形成导管，导致尿路感染。由于保护 生物膜基质和附着细胞的缓慢生长，生物膜细胞的耐药性高达1000倍 比同一物种的浮游细胞比抗菌素。那，凯蒂很难治疗 尤其是在长期使用期间，可能发生阻塞导管管腔，导致石材形成 以及膀胱甚至肾脏的感染。用高剂量的抗菌药物治疗癌症 药物还可以不利地促进多药耐药细菌的发展。尽管很广泛 迄今为止的研究，目前的技术无法提供长期（> 30天）的结垢控制。这个尚未满足 挑战促使我们促使我们设计智能导管，最终放射性cauti。 最近，Pi的实验室制定了一种基于主动地形的新的防污策略 磁性响应式的微米大小柱子以可调频率和力水平击败。这是 通过将Fe3O4纳米颗粒加载到每个支柱的尖端并产生电子 使用嵌入导管壁中的绝缘铜线圈（因此不会改变导管） 轮廓）。这种新颖的设计表现出了前所未有的强大防毒活动，可以抑制 生物膜形成多种物种最多3.6 log（99.98％）48小时，然后去除成熟的生物膜 与平面对照相比，最多可按更强的力按需登录（99.97％）。原型 内壁上有微米大小的柱子的导管进行了设计，并保持清洁30多个 在人造尿液中的日子和尿道疾病大肠杆菌（UPEC）的挑战，而 在5天内，UPEC生物膜完全阻断了平坦和静态对照。这些结果 促使团队进一步开发这项技术，还可以控制外导管墙的生物污染， 由尿道粘膜覆盖，并参与了三分之二的小蛋黄。集成模拟和 将进行实验研究，以了解主动的生物污染控制机制 地形和导管墙两侧的防污地形的设计原理。这 最佳设计将在体内进一步测试，使用UPEC诱导的cauti兔模型。两者都是小牛 将评估预防（长达30天）和去除已建立的生物膜。