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.

导尿管相关性尿路感染（CANTI）是最常见的医疗保健相关性疾病之一， 感染（HAI），在美国的患病率为13 - 15%。此外， 受影响患者的发病率和死亡率增加，估计每年有13，000人死亡。是 众所周知，非生物导管材料易于微生物定植，然后微生物上升 导尿管通过蠕动和生物膜形成，引起尿路感染。因保护 由于生物膜基质和附着细胞的缓慢生长，生物膜细胞的抵抗力高达1,000倍 对抗菌剂的敏感性更高。因此，尿路感染难以治疗， 尤其是在长期使用期间，可能发生导管腔堵塞，导致结石形成 以及膀胱甚至肾脏的感染高剂量抗菌药物治疗尿路感染 药物也会不利地促进多重耐药细菌的发展。尽管进行了广泛 迄今为止的研究表明，目前没有任何技术可以提供长期（>30天）的结垢控制。这一未满足 这一挑战促使我们设计智能导管，以最终根除PatientTI。 最近，PI的实验室开发了一种新的基于主动地形的可调策略， 磁响应微米大小的支柱，以可调的频率和力量水平跳动。这是 通过将Fe 3 O 4纳米颗粒负载在每个柱的尖端上并产生电磁场来实现 使用嵌入导管壁中的绝缘铜线圈（因此不会改变导管 profile）。这种新颖的设计表现出前所未有的强抑制活性， 48小时内多个物种的生物膜形成高达3.6 log（99.98%）并去除成熟的生物膜 与平坦对照相比，在需要时增加高达3.5个对数（99.97%），具有更强的力。一个原型 设计了一种在内壁上具有微米尺寸柱的导管，并且保持清洁超过30 在人工尿流和尿路致病性大肠杆菌（UPEC）的挑战下， 在5天内，平坦和静态对照都被UPEC生物膜完全阻断。这些结果 促使团队进一步开发这项技术，以控制外导管壁的生物污垢， 其被尿道粘膜覆盖，并且涉及三分之二的尿道炎。集成仿真和 通过实验研究，了解活性污泥法控制生物污损的机理。 拓扑结构和导管壁两侧的微结构拓扑结构的设计原则。的 最佳设计将使用由UPEC诱导的兔PTI模型在体内进一步测试。Both 将评估已形成生物膜的预防（最多30天）和去除。