Department of Surgery-Otolaryngology Head and Neck Surgery Adelaide University, South Australia.
Int Forum Allergy Rhinol. 2012 Jul-Aug;2(4):309-15. doi: 10.1002/alr.21038. Epub 2012 Mar 20.
Bacterial biofilms are a major obstacle in management of recalcitrant chronic rhinosinusitis. NVC-422 is a potent, fast-acting, broad-spectrum, nonantibiotic, antimicrobial with a new mechanism of action effective against biofilm bacteria in in vitro conditions. The aim of this study was to investigate the safety and efficacy of NVC-422 as local antibiofilm treatment in a sheep model of rhinosinusitis.
After accessing and occluding frontal sinus ostia in 24 merino sheep via staged endoscopic procedures, S. aureus clinical isolate was instilled in frontal sinuses. Following biofilm formation, ostial obstruction was removed and sinuses irrigated with 0.1% and 0.5% NVC-422 in 5 mM acetate isotonic saline at pH 4.0. Sheep were monitored for adverse effects and euthanized 24 hours after treatment. Frontal sinuses were assessed for infection and changes in mucosa after the treatment. S. aureus biofilms were identified with Baclight-confocal scanning microscopy protocol and the biofilm biomass assayed by applying the COMSTAT2 program to recorded image stacks.
After 2 irrigations with 0.1% NVC-422, S. aureus biofilm biomass was reduced when compared to control sinuses (p = 0.0001), though this effect was variable in samples. NVC-422 0.5% solution irrigations reduced biofilm even more significantly and consistently over all samples (p < 0.0001). NVC-422 0.5% was also more effective than 0.1% NVC-422, vehicle control, and normal saline sinus irrigations in reducing biofilm biomass (p < 0.05 for all subgroups). No adverse events were observed in sheep after sinus irrigations with 0.1% and 0.5% NVC-422 solutions.
NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis.
细菌生物膜是治疗难治性慢性鼻-鼻窦炎的主要障碍。NVC-422 是一种强效、快速作用、广谱、非抗生素、具有新作用机制的抗菌药物，在体外条件下对生物膜细菌有效。本研究旨在研究 NVC-422 作为局部抗生物膜治疗在绵羊慢性鼻-鼻窦炎模型中的安全性和疗效。
通过分期内镜手术进入并阻塞 24 只美利奴羊的额窦窦口，将金黄色葡萄球菌临床分离株注入额窦。形成生物膜后，去除窦口阻塞并使用 0.1%和 0.5%的 NVC-422 在 pH4.0 的 5mM 醋酸等渗盐水中冲洗鼻窦。监测绵羊是否有不良反应，并在治疗后 24 小时安乐死。治疗后评估额窦感染和粘膜变化。使用 Baclight-共聚焦扫描显微镜方案鉴定金黄色葡萄球菌生物膜，并通过应用 COMSTAT2 程序对记录的图像堆栈进行生物膜生物量测定。
与对照窦相比，用 0.1%NVC-422 冲洗 2 次后，金黄色葡萄球菌生物膜生物量减少（p = 0.0001），但在样本中这种作用是可变的。用 0.5%NVC-422 溶液冲洗更显著且一致地减少生物膜，所有样本均如此（p < 0.0001）。与 0.1%NVC-422、载体对照和生理盐水窦冲洗相比，0.5%NVC-422 溶液在减少生物膜生物量方面更有效（所有亚组的 p < 0.05）。绵羊用 0.1%和 0.5%NVC-422 溶液冲洗鼻窦后未观察到不良反应。
NVC-422 是一种有效的金黄色葡萄球菌生物膜局部治疗药物，在该生物膜相关鼻窦炎动物模型中具有剂量依赖性疗效。
