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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 Ong
Research Paper

Abstract

Purpose

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.

Method

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.

Results

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.

Conclusions

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.

KEY WORDS

biofilm ciprofloxacin inhalation mannitol respiratory tract infection 

ABBREVIATIONS

ACI

Anderson cascade impactor

ATCC

American type cell culture collection

BE

Bronchiectasis

CAMHB

Cation adjusted Mueller-Hinton broth

Cipro

Ciprofloxacin only

Cipro-man

Ciprofloxacin and mannitol

CDC

Centers for disease control

CF

Cystic fibrosis

CFU

Colony-forming unit count

COPD

Chronic obstructive pulmonary disease

CV

Crystal violet

DMEM

Dulbecco’s Modified Eagle’s Medium

DMSO

Dimethyl sulfoxide

EPS

Extracellular polymeric substances

EVOM

Epithelial voltohmmeter

f1

Difference factor

f2

Similarity factor

FBS

Fetal bovine serum

FPF

Fine particle fraction

GSD

Geometric standard deviation

HBSS

Hank’s balanced salt solution

HPLC

High performance liquid chromatography

LB

Luria-Bertani

MMAD

Mass median aerodynamic diameter

P. aeruginosa

Pseudomonas aeruginosa

PBS

Phosphate buffered saline

PCF

Primary ciliary dyskinesia

RID

Refractive index detector

RTIs

Respiratory tract infections

SEM

Scanning electron microscope

TEER

Transepithelial electrical resistance

USP

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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