Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
Antimicrob Agents Chemother. 2012 Dec;56(12):6095-103. doi: 10.1128/AAC.01173-12. Epub 2012 Sep 4.
The use of percutaneous medical devices often results in nosocomial infections. Attachment of microorganisms to the surfaces of these medical devices triggers biofilm formation, which presents significant complications to the health of a patient and may lead to septicemia, thromboembolism, or endocarditis if not correctly treated. Although several antimicrobials are commonly used for prevention of biofilm formation, they have limited efficacy against formed biofilms. In this study, we report the use of an enzymatic, gaseous nitric oxide (gNO)-releasing dressing for the prevention and treatment of Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa biofilms. Results show that the bactericidal activity against biofilms of the test strains was dependent on time and rate of gNO release from the dressing. Following 6 h of treatment, gNO-releasing dressings significantly inhibited the growth of test strains relative to vehicle control dressings, demonstrating eradication of bacterial concentrations of up to 10(5) CFU/cm(2). Complete cell death was observed for both prevention of biofilm formation and treatment of 24-h-grown biofilms after 6 h of treatment with the gNO-releasing dressings. Further, gNO-releasing dressings were more efficient against formed biofilms than other antimicrobial agents currently used. These results demonstrate that the gNO-releasing dressing can produce sufficient levels of gNO over a therapeutically relevant duration for maximal bactericidal effects against virulent bacterial strains known to cause nosocomial infections.
经皮医疗装置的使用常导致医院获得性感染。微生物附着在这些医疗装置的表面会引发生物膜形成,如果不加以正确治疗,这会给患者的健康带来严重并发症,并可能导致败血症、血栓栓塞或心内膜炎。尽管几种抗生素常用于预防生物膜形成,但它们对已形成的生物膜的效果有限。在这项研究中,我们报告了一种酶促、气态一氧化氮(gNO)释放敷料在预防和治疗鲍曼不动杆菌、耐甲氧西林金黄色葡萄球菌和铜绿假单胞菌生物膜方面的应用。结果表明,测试菌株生物膜的杀菌活性取决于敷料中 gNO 的释放速度和时间。经过 6 小时的治疗,gNO 释放敷料显著抑制了测试菌株的生长,与载体对照敷料相比,抑制了高达 10(5)CFU/cm(2)的细菌浓度。在用 gNO 释放敷料治疗 24 小时形成的生物膜 6 小时后,不仅可以预防生物膜形成,还可以完全杀死生物膜中的细胞。此外,gNO 释放敷料对已形成的生物膜的效果优于目前使用的其他抗菌剂。这些结果表明,gNO 释放敷料可以在治疗相关的时间内产生足够水平的 gNO,从而对已知引起医院获得性感染的致病细菌菌株产生最大杀菌效果。