title: The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?
abstract: Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree.
  
  
  
  To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF.
  
  
  
  Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included.
  
  
  
  35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics.
  
  
  
  After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa.
authors.affiliation: Department of Paediatric Pulmonology and Allergology, Erasmus Medical Centre (MC) - Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: a.c.bos@erasmusmc.nl.
authors.forename: Aukje C
authors.initials: AC
authors.lastname: Bos
authors.affiliation: Department of Paediatric Pulmonology and Allergology, Erasmus Medical Centre (MC) - Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: 328867kp@student.eur.nl.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Passé
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: jwmouton@gmail.com.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.affiliation: Department of Paediatric Pulmonology and Allergology, Erasmus Medical Centre (MC) - Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: h.janssens@erasmusmc.nl.
authors.forename: Hettie M
authors.initials: HM
authors.lastname: Janssens
authors.affiliation: Department of Paediatric Pulmonology and Allergology, Erasmus Medical Centre (MC) - Sophia Children's Hospital, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: h.tiddens@erasmusmc.nl.
authors.forename: Harm A W M
authors.initials: HA
authors.lastname: Tiddens
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D014018:Tissue Distribution; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: Alginate; Cystic fibrosis; Inhaled antibiotics; Pseudomonas aeruginosa; Sputum binding