title: Biofilm-dependent airway infections: a role for ambroxol?
abstract: Biofilms are a key factor in the development of both acute and chronic airway infections. Their relevance is well established in ventilator associated pneumonia, one of the most severe complications in critically ill patients, and in cystic fibrosis, the most common lethal genetic disease in Caucasians. Accumulating evidence suggests that biofilms could have also a role in chronic obstructive pulmonary disease and their involvement in bronchiectasis has been proposed as well. When they grow in biofilms, microorganisms become multidrug-resistant. Therefore the treatment of biofilm-dependent airway infections is problematic. Indeed, it still largely based on measures aiming to prevent the formation of biofilms or remove them once that they are formed. Here we review recent evidence suggesting that the mucokinetic drug ambroxol has specific anti-biofilm properties. We also discuss how additional pharmacological properties of this drug could be beneficial in biofilm-dependent airway infections. Specifically, we review the evidence showing that: 1-ambroxol exerts anti-inflammatory effects by inhibiting at multiple levels the activity of neutrophils, and 2-it improves mucociliary clearance by interfering with the activity of airway epithelium ion channels and transporters including sodium/bicarbonate and sodium/potassium/chloride cotransporters, cystic fibrosis transmembrane conductance regulator and aquaporins. As a whole, the data that we review here suggest that ambroxol could be helpful in biofilm-dependent airway infections. However, considering the limited clinical evidence available up to date, further clinical studies are required to support the use of ambroxol in these diseases.
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University of Naples, Via Pansini 5, 80131 Napoli, Italy. Electronic address: cataldi@unina.it.
authors.forename: M
authors.initials: M
authors.lastname: Cataldi
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University of Naples, Via Pansini 5, 80131 Napoli, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Sblendorio
authors.affiliation: Department of Health Sciences, University Magna Græcia of Catanzaro, University Campus "Salvatore Venuta", Viale Europa, I-88100 Catanzaro, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Leo
authors.affiliation: University of Salerno, Via Allende, 84081 Baronissi, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Piazza
mesh_terms: D000551:Ambroxol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D005100:Expectorants / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000893:Anti-Inflammatory Agents; D005100:Expectorants; D000551:Ambroxol
keywords: Ambroxol; Ambroxol hydrochloride (PubChem CID: 108013); Biofilm; Bronchiectasis; Chronic obstructive pulmonary disease; Cystic fibrosis; Ventilator-associated pneumonia