title: Effect of ambroxol on pneumonia caused by Pseudomonas aeruginosa 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neonatology, Children's Hospital of Chongqing Medical University, Key Laboratory of Developmental Diseases in Childhood, Chongqing Medical University, Ministry of Education, Chongqing, China.
authors: Fang
authors: F
authors: Li
authors: Wenlei
authors: W
authors: Wang
authors: Linyan
authors: L
authors: Hu
authors: Luquan
authors: L
authors: Li
authors: Jialin
authors: J
authors: Yu
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D058491:Bacterial Load; D018441:Biofilms / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007442:Intubation, Intratracheal; D008168:Lung / Q000382:microbiology / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053717:Pneumonia, Ventilator-Associated / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D016753:Interleukin-10; D000551:Ambroxol; D007371:Interferon-gamma