Nitric Oxide-Releasing Insert for Disinfecting the Hub Region of Tunnel Dialysis Catheters

作者：Joshua C. Doverspike, Shale J. Mack, Amy Luo, Blake Stringer, Shelby Reno, Marie S. Cornell, Álvaro Rojas-Peña, Jianfeng Wu, Chuanwu Xi, Alexander S. Yevzlin, Mark E. Meyerhoff · 发表于：ACS Applied Materials & Interfaces · 年份：2020 · DOI：10.1021/acsami.0c13230 · 被引用次数：18 · 研究领域：Central Venous Catheters and Hemodialysis、Acute Kidney Injury Research、Antibiotics Pharmacokinetics and Efficacy

The use of tunneled dialysis catheters (TDCs) for patients in need of hemodialysis treatments (HDs) causes a significant number of bloodstream infections (BSIs), with very few viable preventative/treatment methods. Use of antibiotics is relatively ineffective due to the development of multidrug-resistant bacterial strains and the inability to penetrate bacterial biofilms. Nitric oxide (NO) is an endogenous gas molecule that has broad-spectrum antimicrobial/antibiofilm activity. In this study, the potential of creating a NO-releasing insert device that is attached onto the hub region cap of TDCs and locally releases NO within the TDC hub is evaluated for its antimicrobial/antibiofilm effectiveness. The NO-releasing insert contains the natural NO donor S -nitrosoglutathione (GSNO), along with zinc oxide (ZnO) nanoparticles to accelerate NO release from the GSNO, within a short silicone tube that is sealed at both ends and attached to the catheter cap. An in vitro 3-d-long antimicrobial study using catheter hubs yielded >6.6 log reductions of both Pseudomonas aeruginosa and Staphylococcus aureus for the NO-releasing insert device compared to controls. Two 14-d-long sheep studies demonstrated that the NO-releasing insert devices are exceptionally potent at preventing bacteria/biofilm growth on the inner lumen walls of TDCs compared to controls that have no preventative treatment devices as well as implanted TDCs that have commercially available chlorhexidine-treated insert device...