在阐明高渗盐水对囊性纤维化患者铜绿假单胞菌作用方面取得的进展。
Advances toward the elucidation of hypertonic saline effects on Pseudomonas aeruginosa from cystic fibrosis patients.
作者信息
Michon Anne-Laure, Jumas-Bilak Estelle, Chiron Raphaël, Lamy Brigitte, Marchandin Hélène
机构信息
UMR 5119 ECOSYM, Equipe Pathogènes et Environnements, U.F.R. des Sciences Pharmaceutiques et Biologiques, Université Montpellier 1, Montpellier, France ; Laboratoire de Bactériologie, Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France.
UMR 5119 ECOSYM, Equipe Pathogènes et Environnements, U.F.R. des Sciences Pharmaceutiques et Biologiques, Université Montpellier 1, Montpellier, France ; Laboratoire d'Hygiène hospitalière, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France.
出版信息
PLoS One. 2014 Feb 28;9(2):e90164. doi: 10.1371/journal.pone.0090164. eCollection 2014.
OBJECTIVES
Nebulized hypertonic saline (HTS) has beneficial effects including reducing pulmonary exacerbations in Cystic Fibrosis (CF) patients. Several mechanisms may explain these effects but antimicrobial activity of NaCl remains largely unexplored. We aimed to measure the antimicrobial effect of NaCl on Pseudomonas aeruginosa isolated from the respiratory tract in CF patients.
METHODS
NaCl minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined for strains characterized for mucoidy, antimicrobial resistance, and ability to form biofilm using 0,9% to 15% NaCl solutions. NaCl effects on biofilm formation, preformed biofilm, and mobility were evaluated. Kinetics of antimicrobial effects was studied.
RESULTS
The growth of all isolates (n = 85) from 34 patients was inhibited by 6% NaCl solution. A 10% concentration had a bactericidal activity on 90% of the isolates. Mucoid and multidrug resistant (MDR) isolates displayed lower MICs compared to non-mucoid and to non-MDR isolates, respectively. Time-kill kinetics showed that NaCl exhibited a rapid, dose and growth phase dependent bactericidal effect. Three percent or more of NaCl inhibited biofilm formation for 69% of strongly adherent isolates. A dose-dependent decrease of preformed biofilm viability and an inhibitory activity on bacterial motility were observed.
CONCLUSIONS
NaCl inhibited the growth of all isolates and killed 38% of tested isolates within concentration range currently used in therapeutics. Our results suggest that anti-pseudomonal activity is another mechanism of action of HTS to add to those already established. Clinical trials are needed to compare diverse HTS conditions of use (rhythm, dose and mode of delivery) to obtain efficient and optimized anti-P. aeruginosa effects. More generally, NaCl effect on other opportunistic pathogens as well as on global microbiotae recovered during polymicrobial diseases warrants further investigations.
目的
雾化高渗盐水（HTS）具有有益作用，包括减少囊性纤维化（CF）患者的肺部加重。有几种机制可以解释这些作用，但NaCl的抗菌活性在很大程度上尚未得到探索。我们旨在测量NaCl对从CF患者呼吸道分离出的铜绿假单胞菌的抗菌作用。
方法
使用0.9%至15%的NaCl溶液，对具有黏液样性、抗菌耐药性和形成生物膜能力的菌株测定NaCl的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）。评估NaCl对生物膜形成、预先形成的生物膜和运动性的影响。研究抗菌作用的动力学。
结果
34例患者的所有分离株（n = 85）的生长均受到6% NaCl溶液的抑制。10%的浓度对90%的分离株具有杀菌活性。黏液样和多重耐药（MDR）分离株分别比非黏液样和非MDR分离株显示出更低的MIC。时间-杀菌动力学表明，NaCl表现出快速、剂量和生长阶段依赖性的杀菌作用。3%或更高浓度的NaCl对69%的强黏附分离株的生物膜形成有抑制作用。观察到预先形成的生物膜活力呈剂量依赖性下降以及对细菌运动性的抑制活性。
结论
NaCl在目前治疗中使用的浓度范围内抑制了所有分离株的生长，并杀死了38%的测试分离株。我们的结果表明，抗铜绿假单胞菌活性是HTS的另一种作用机制，可补充已确定的机制。需要进行临床试验以比较不同的HTS使用条件（频率、剂量和给药方式），以获得有效的、优化的抗铜绿假单胞菌效果。更普遍地说，NaCl对其他机会性病原体以及在多微生物疾病期间恢复的整体微生物群的影响值得进一步研究。
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