Effect of Ambroxol on Pneumonia Caused by <i>Pseudomonas aeruginosa</i> with Biofilm Formation in an Endotracheal Intubation Rat Model

Abstract

Background:Pseudomonas aeruginosa, especially the mucoid phenotype, is responsible for most of the morbidity and mortality in ventilator-associated pneumonia. Although ambroxol is widely used in neonatal lung problems as a mucolytic as well as an antioxidant agent, its anti-infective role is not well demonstrated by studies in vivo. Objective: To explore the effect of ambroxol on the biofilms of mucoid P. aeruginosa and on the associated lung infection using a rat model. Methods: We developed a rat model of acute lung infection by endotracheal intubation with a tube covered with mucoid P. aeruginosa biofilm. Then, we studied the effect of ambroxol on the biofilm using saline treatment as a control. Subsequently, we studied the microstructure of the biofilm, bacterial count in the tubes and lungs, pathological changes that occurred in the lungs, and the cytokine response. Results: Alteration of the microstructure of the biofilm with ambroxol treatment was demonstrated by scanning electron microscopy. The bacterial counts on the biofilm-covered tube in the ambroxol-treated group were significantly lower than those in the saline-treated group on both post-bacterial challenge days 4 and 7 (p < 0.05). The bacterial counts in lungs of the ambroxol-treated group and of the saline-treated group on post-bacterial challenge day 7 were not significantly different (p > 0.05). The pathological changes in lungs were milder with the effect of ambroxol. The cytokine responses, namely the level of IFN-γ and the ratio of IFN-γ and IL-10, were also reduced with the effect of ambroxol. Conclusion: We demonstrated that the ambroxol treatment could destroy the structure of the biofilm on the tube used for intubation and decrease the bacterial load. Further, the reduced cytokine response and milder pathological changes in lungs in an endotracheal intubation rat model indicate that ambroxol can attenuate the damage caused by biofilm-associated infection in the lung.

Effects of Combined Treatment with Ambroxol and Ciprofloxacin on Catheter-Associated <b><i>Pseudomonas aeruginosa</i></b> Biofilms in a Rat Model

“…The method used for bacterial biofilm formation was described previously by Li et al [10]. Briefly, the bacteria were preincubated in Luria broth overnight at 37°C, washed three times with saline and resuspended in the same solution at 10 9 CFU/ml.…”

“…Infection was induced in rats using the method described previously by Li et al [10]. Rats were placed in an exposure chamber (length × width × height: 40 × 30 × 34 cm) to be exposed to drugs.…”

“…Eight randomly selected rats in each of the intubated groups were prepared for quantitative bacteriology [10]. The intubation tubes were removed under aseptic technique and cut open longitudinally.…”

The Place Of Mucolytics In The treatment Of Inflammatory Respiratory Diseases

“…В экспериментальном исследовании на живот-ных было изученовлияние амброксола на био-пленки, сформированные мукоиднымиштаммами Pseudomonas aeruginosa [18]. Показано нарушение микроструктуры биопленок после использования амброксола.…”

Role of mucoactive drugs in treatment of chronic obstructive pulmonary disease

“…Влияние амброксола на биопленки В недавно проведенном исследовании F.Li et al на животных моделях были изучены эффекты амброк сола на биопленки, сформированные мукоидными штаммами Pseudomonas aeruginosa [43]. Электронная микроскопия продемонстрировала нарушение мик роструктуры биопленок после использования амб роксола.…”