Abstract
ObjectivesNebulized 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.MethodsNaCl 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.ResultsThe 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.ConclusionsNaCl 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.
Highlights
Cystic fibrosis (CF) is the most common inherited disease in Caucasians
NaCl displayed a bactericidal effect, 38% of the CF isolates being killed by a 7% NaCl solution, concentration currently used in therapeutics, 50% and 90% of the isolates being killed by 8% and 10% of NaCl, respectively
We proposed the first study evaluating in vitro NaCl activity on a large population of P. aeruginosa isolated from CF patients
Summary
Cystic fibrosis (CF) is the most common inherited disease in Caucasians. The disorder is initiated by a defect in the CF transmembrane conductance regulator (CFTR) gene coding for an apical membrane chloride channel mediating transepithelial salt and liquid movement [1]. The volume of the airway surface liquid hypothesis suggesting that CFTR defect leads to water loss related to sodium chloride (NaCl) depletion in the mucus remains the main hypothesis [1,4]. According to this hypothesis, immotile dehydrated plugs are formed leading to inefficient mucociliary clearance that allows bacteria to cause lung infection [4]. Immotile dehydrated plugs are formed leading to inefficient mucociliary clearance that allows bacteria to cause lung infection [4] This mechanism suggested that hypertonic saline (HTS) nebulization could favor mucociliary clearance [5]. Testing HTS on a large population of P. aeruginosa CF isolates should elucidate the anti-microbial effect of NaCl
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