Moore Jessica V, Kim Doyoung, Irwin Nicola J, Rimer Jeffrey D, McCoy Colin P
School of Pharmacy, Queen's University Belfast 97 Lisburn Road Belfast BT9 7BL Northern Ireland UK
Department of Chemical and Biomolecular Engineering, University of Houston Houston TX 77204 USA.
RSC Adv. 2023 Jan 11;13(4):2202-2212. doi: 10.1039/d2ra06418a.
Long-term catheterised individuals are at significant risk of developing catheter-associated urinary tract infections (CAUTIs), with up to 50% of patients experiencing recurrent episodes of catheter encrustation and blockage. Catheter blockage is a result of accumulation of carbonate apatite and struvite formed upon precipitation of ions within urine due to an infection-induced rise in pH. The aim of this study was to investigate the antimicrobial and anti-encrustation activities of tetrasodium ethylenediaminetetraacetic acid (tEDTA) to evaluate its potential efficacy in preventing CAUTIs and catheter blockages. The antimicrobial activity of tEDTA against uropathogens was assessed using time kill assays performed in artificial urine (AU). Crystallisation studies and bladder model assays were conducted to investigate the effect of tEDTA on struvite crystallisation and catheter blockage. tEDTA displayed bacteriostatic activity against and prevented precipitation of ions in the AU. Crystallisation studies confirmed tEDTA inhibits struvite nucleation and growth Mg chelation with 7.63 mM tEDTA, equimolar to the concentration of divalent cations in AU, preventing the formation of crystalline deposits and blockage of Foley catheters for ≥168 h. The promising chelating abilities of low tEDTA concentrations could be exploited to inhibit encrustation and blockage of indwelling catheters. The fundamental research presented will inform our future development of an effective tEDTA-eluting catheter coating aimed at preventing catheter encrustation.
长期使用导尿管的个体发生导管相关尿路感染(CAUTIs)的风险很高,高达50%的患者会反复出现导管结壳和堵塞情况。导管堵塞是由于感染导致尿液pH值升高,尿液中的离子沉淀形成碳酸磷灰石和鸟粪石积聚所致。本研究的目的是调查乙二胺四乙酸四钠(tEDTA)的抗菌和抗结壳活性,以评估其在预防CAUTIs和导管堵塞方面的潜在疗效。使用在人工尿液(AU)中进行的时间杀灭试验评估tEDTA对尿路病原体的抗菌活性。进行了结晶研究和膀胱模型试验,以研究tEDTA对鸟粪石结晶和导管堵塞的影响。tEDTA在AU中显示出抑菌活性并防止离子沉淀。结晶研究证实,tEDTA通过与7.63 mM的tEDTA进行镁螯合(与AU中二价阳离子浓度等摩尔)抑制鸟粪石成核和生长,防止结晶沉积物的形成和Foley导管堵塞≥168小时。低浓度tEDTA有前景的螯合能力可用于抑制留置导管的结壳和堵塞。所呈现的基础研究将为我们未来开发旨在防止导管结壳的有效tEDTA洗脱导管涂层提供参考。