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Pseudomonas aeruginosa  forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with  P. aeruginosa  and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on  P. aeruginosa  biofilm. We show that azithromycin exhibited a potent activity against  P. aeruginosa  biofilm, and microscopic observation revealed that azithromycin substantially inhibited the formation of solid surface biofilms. Interestingly, we observed that azithromycin restricted  P. aeruginosa  biofilm formation by inhibiting the expression of  pel  genes, which has been previously shown to play an essential role in bacterial attachment to solid-surface biofilm. In a rat model of chronic  P. aeruginosa  lung infection, we show that azithromycin treatment resulted in the suppression of quorum sensing-regulated virulence factors, significantly improving the clearance of  P. aeruginosa  biofilms compared to that in the placebo control. We conclude that azithromycin attenuates  P. aeruginosa  biofilm formation, impairs its ability to produce extracellular biofilm matrix, and increases its sensitivity to the immune system, which may explain the clinical efficacy of azithromycin in cystic fibrosis patients.

Azithromycin Exhibits Activity Against Pseudomonas aeruginosa in Chronic Rat Lung Infection Model