title: The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections.
abstract: In airway infections, biofilm formation has been demonstrated to be responsible for both acute and chronic events, and constitutes a genuine challenge in clinical practice. Difficulty in eradicating biofilms with systemic antibiotics has led clinicians to consider the possible role of non-antibiotic therapy. The aim of this review is to examine current evidence for the use of N-acetylcysteine (NAC) in the treatment of biofilm-related respiratory infections.
  
  
  
  Electronic searches of PUBMED up to September 2015 were conducted, searching for 'biofilm', 'respiratory tract infection', 'N-acetylcysteine', 'cystic fibrosis', 'COPD', 'bronchiectasis', 'otitis', and 'bronchitis' in titles and abstracts. Studies included for review were primarily in English, but a few in Italian were also selected.
  
  
  
  Biofilm formation may be involved in many infections, including ventilator-associated pneumonia, cystic fibrosis, bronchiectasis, bronchitis, and upper respiratory airway infections. Many in vitro studies have demonstrated that NAC is effective in inhibiting biofilm formation, disrupting preformed biofilms (both initial and mature), and reducing bacterial viability in biofilms. There are fewer clinical studies on the use of NAC in disruption of biofilm formation, although there is some evidence that NAC alone or in combination with antibiotics can decrease the risk of exacerbations of chronic bronchitis, chronic obstructive pulmonary disease, and rhinosinusitis. However, the usefulness of NAC in the treatment of cystic fibrosis and bronchiectasis is still matter of debate. Most of the studies published to date have used oral or intramuscular NAC formulations.
  
  
  
  Evidence from in vitro studies indicates that NAC has good antibacterial properties and the ability to interfere with biofilm formation and disrupt biofilms. Results from clinical studies have provided some encouraging findings that need to be confirmed and expanded using other routes of administration of NAC such as inhalation.
authors: Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Francesco
authors: F
authors: Blasi
authors: The Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, United Kingdom.
authors: Clive
authors: C
authors: Page
authors: Department of Experimental and Clinical Medicine, University of Florence, Careggi University Hospital, Florence, Italy; Clinical Microbiology and Virology Unit, Careggi University Hospital, Florence, Italy; Department of Medical Biotechnologies, University of Siena, Santa Maria alle Scotte University Hospital, Siena, Italy; Don Carlo Gnocchi Foundation, Florence, Italy.
authors: Gian Maria
authors: GM
authors: Rossolini
authors: Department of Medical Biotechnologies, University of Siena, Santa Maria alle Scotte University Hospital, Siena, Italy.
authors: Lucia
authors: L
authors: Pallecchi
authors: Department of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, Italy.
authors: Maria Gabriella
authors: MG
authors: Matera
authors: University of Rome Tor Vergata, Department of Systems Medicine, Rome, Italy; University Hospital Tor Vergata, Unit of Respiratory Medicine, Rome, Italy.
authors: Paola
authors: P
authors: Rogliani
authors: University of Rome Tor Vergata, Department of Systems Medicine, Rome, Italy. Electronic address: mario.cazzola@uniroma2.it.
authors: Mario
authors: M
authors: Cazzola
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000280:Administration, Inhalation; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D001987:Bronchiectasis / Q000150:complications / Q000188:drug therapy; D001991:Bronchitis / Q000150:complications / Q000188:drug therapy; D029481:Bronchitis, Chronic / Q000150:complications / Q000188:drug therapy; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy; D005100:Expectorants / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy; D012141:Respiratory Tract Infections / Q000150:complications / Q000188:drug therapy*
chemical_list: D005100:Expectorants; D000111:Acetylcysteine
keywords: Airways infections; Biofilm; Inhaled formulation; N-acetylcysteine; Topical administration