Gruber Martina, Moser Ivan, Nagl Markus, Lackner Michaela
Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02527-16. Print 2017 May.
Lung infections with multiresistant pathogens are a major problem among patients suffering from cystic fibrosis (CF). -Chlorotaurine (NCT), a microbicidal active chlorine compound with no development of resistance, is well tolerated upon inhalation. The aim of this study was to investigate the bactericidal and fungicidal activity of NCT in artificial sputum medium (ASM), which mimics the composition of CF mucus. The medium was inoculated with bacteria (, including some methicillin-resistant [MRSA] strains, , and ) or spores of fungi (, , , , , , , , , and sp.), to final concentrations of 10 to 10 CFU/ml. NCT was added at 37°C, and time-kill assays were performed. At a concentration of 1% (10 mg/ml, 55 mM) NCT, bacteria and spores were killed within 10 min and 15 min, respectively, to the detection limit of 10 CFU/ml (reduction of 5 to 6 log units). Reductions of 2 log units were still achieved with 0.1% (bacteria) and 0.3% (fungi) NCT, largely within 10 to 30 min. Measurements by means of iodometric titration showed oxidizing activity for 1, 30, 60, and >60 min at concentrations of 0.1%, 0.3%, 0.5%, and 1.0% NCT, respectively, which matches the killing test results. NCT demonstrated broad-spectrum microbicidal activity in the milieu of CF mucus at concentrations ideal for clinical use. The microbicidal activity of NCT in ASM was even stronger than that in buffer solution; this was particularly pronounced for fungi. This finding can be explained largely by the formation, through transhalogenation, of monochloramine, which rapidly penetrates pathogens.
多重耐药病原体引起的肺部感染是囊性纤维化（CF）患者面临的一个主要问题。氯牛磺酸（NCT）是一种不会产生耐药性的具有杀菌活性的氯化合物，吸入后耐受性良好。本研究的目的是研究NCT在模拟CF黏液成分的人工痰液培养基（ASM）中的杀菌和杀真菌活性。该培养基接种细菌（包括一些耐甲氧西林金黄色葡萄球菌[MRSA]菌株、铜绿假单胞菌和鲍曼不动杆菌）或真菌孢子（烟曲霉、黄曲霉、土曲霉、黑曲霉、构巢曲霉、白念珠菌、热带念珠菌、近平滑念珠菌、光滑念珠菌和新生隐球菌），最终浓度为10⁵至10⁷CFU/ml。在37°C下加入NCT，并进行时间杀菌试验。在NCT浓度为1%（10mg/ml，55mM）时，细菌和孢子分别在10分钟和15分钟内被杀灭至检测限10²CFU/ml（降低5至6个对数单位）。使用0.1%（针对细菌）和0.3%（针对真菌）的NCT仍能在很大程度上在10至30分钟内实现2个对数单位的降低。通过碘量滴定法测量显示，在NCT浓度分别为0.1%、0.3%、0.5%和1.0%时，其氧化活性分别持续1、30、60和>60分钟，这与杀菌试验结果相符。NCT在适合临床使用的浓度下，在CF黏液环境中表现出广谱杀菌活性。NCT在ASM中的杀菌活性甚至比在缓冲溶液中更强；对真菌而言尤其明显。这一发现很大程度上可以通过通过卤素转移形成的一氯胺来解释，一氯胺能迅速穿透病原体。
