Rani Suriani Abdul, Celeri Chris, Najafi Ron, Bley Keith, Debabov Dmitri
NovaBay Pharmaceuticals, Inc., 5980 Horton Street, Suite 550, Emeryville, CA, 94608, USA.
Urolithiasis. 2016 Jun;44(3):247-56. doi: 10.1007/s00240-015-0811-3. Epub 2015 Aug 18.
Long-term use of indwelling urinary catheters can lead to urinary tract infections and loss of catheter patency due to encrustation and blockage. Encrustation of urinary catheters is due to formation of crystalline biofilms by urease-producing microorganisms such as Proteus mirabilis. An in vitro catheter biofilm model (CBM) was used to evaluate current methods for maintaining urinary catheter patency. We compared antimicrobial-coated urinary Foley catheters, with both available catheter irrigation solutions and investigational solutions containing NVC-422 (N,N-dichloro-2,2-dimethyltaurine; a novel broad-spectrum antimicrobial). Inoculation of the CBM reactor with 10(8) colony-forming units of P. mirabilis resulted in crystalline biofilm formation in catheters by 48 h and blockage of catheters within 5 days. Silver hydrogel or nitrofurazone-coated catheters did not extend the duration of catheter patency. Catheters irrigated daily with commercially available solutions such as 0.25 % acetic acid and isotonic saline blocked at the same rate as untreated catheters. Daily irrigations of catheters with 0.2 % NVC-422 in 10 mM acetate-buffered saline pH 4 or Renacidin maintained catheter patency throughout 10-day studies, but P. mirabilis colonization of the CBM remained. In contrast, 0.2 % NVC-422 in citrate buffer (6.6 % citric acid at pH 3.8) resulted in an irrigation solution that not only maintained catheter patency for 10 days but also completely eradicated the P. mirabilis biofilm within one treatment day. These data suggest that an irrigation solution containing the rapidly bactericidal antimicrobial NVC-422 in combination with citric acid to permeabilize crystalline biofilm may significantly enhance catheter patency versus other approved irrigation solutions and antimicrobial-coated catheters.
长期使用留置导尿管会导致尿路感染,以及由于结壳和堵塞而使导尿管失去通畅性。导尿管结壳是由产脲酶微生物(如奇异变形杆菌)形成结晶生物膜所致。采用体外导尿管生物膜模型(CBM)来评估目前维持导尿管通畅的方法。我们将抗菌涂层的弗利氏导尿管与现有的导尿管冲洗液以及含有NVC - 422(N,N - 二氯 - 2,2 - 二甲基牛磺酸;一种新型广谱抗菌剂)的研究用溶液进行了比较。在CBM反应器中接种10⁸个奇异变形杆菌菌落形成单位,48小时内导尿管中形成结晶生物膜,5天内导尿管堵塞。水凝胶银或呋喃西林涂层的导尿管并未延长导尿管通畅的持续时间。每天用市售溶液(如0.25%乙酸和等渗盐水)冲洗的导尿管与未处理的导尿管堵塞速率相同。在为期10天的研究中,每天用pH值为4的10 mM乙酸盐缓冲盐水中的0.2% NVC - 422或雷尼替丁冲洗导尿管可维持其通畅性,但CBM中仍存在奇异变形杆菌定植。相比之下,柠檬酸盐缓冲液(pH值为3.8的6.6%柠檬酸)中的0.2% NVC - 422产生的冲洗液不仅能使导尿管在10天内保持通畅,还能在一个治疗日内完全根除奇异变形杆菌生物膜。这些数据表明,与其他已批准的冲洗液和抗菌涂层导尿管相比,含有快速杀菌抗菌剂NVC - 422并结合柠檬酸以渗透结晶生物膜的冲洗液可能会显著提高导尿管的通畅性。