Pharmaceutical Research

, 35:50 | Cite as

Sweetening Inhaled Antibiotic Treatment for Eradication of Chronic Respiratory Biofilm Infection

  • Ching-Yee Loo
  • Wing-Hin Lee
  • Gianluca Lauretani
  • Santo Scalia
  • David Cipolla
  • Daniela Traini
  • Paul Young
  • Hui Xin OngEmail author
Research Paper



The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm.


Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy.


Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone.


The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.


biofilm ciprofloxacin inhalation mannitol respiratory tract infection 



Anderson cascade impactor


American type cell culture collection




Cation adjusted Mueller-Hinton broth


Ciprofloxacin only


Ciprofloxacin and mannitol


Centers for disease control


Cystic fibrosis


Colony-forming unit count


Chronic obstructive pulmonary disease


Crystal violet


Dulbecco’s Modified Eagle’s Medium


Dimethyl sulfoxide


Extracellular polymeric substances


Epithelial voltohmmeter


Difference factor


Similarity factor


Fetal bovine serum


Fine particle fraction


Geometric standard deviation


Hank’s balanced salt solution


High performance liquid chromatography




Mass median aerodynamic diameter

P. aeruginosa

Pseudomonas aeruginosa


Phosphate buffered saline


Primary ciliary dyskinesia


Refractive index detector


Respiratory tract infections


Scanning electron microscope


Transepithelial electrical resistance


United States Pharmacopoeia


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical SchoolThe University of SydneySydneyAustralia
  2. 2.Faculty of Pharmacy and Health Sciences, Royal College of Medicine PerakUniversiti Kuala Lumpur (RCMP UniKL)IpohMalaysia
  3. 3.Department of Chemical and Pharmaceutical SciencesUniversity of FerraraFerraraItaly
  4. 4.Pharmaceutical SciencesAradigm CorporationHaywardUSA
  5. 5.Discipline of PharmacologySydney Medical SchoolCamperdownAustralia

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