Synergy of nebulized phage PEV20 and ciprofloxacin combination against Pseudomonas aeruginosa

Synergy of nebulized phage PEV20 and ciprofloxacin combination against Pseudomonas aeruginosa.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: International Journal of Pharmaceutics
Volume: 551
Number: 1-2
Page Range: pp. 158-165
Date: 2018
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.ijpharm.2018.09.024
ISSN: 03785173
Date Deposited: 03 Jan 2021 22:59

Nebulization is currently used for delivery of antibiotics for respiratory infections. Bacteriophages (or phages) are effective predators of pathogens including Pseudomonas aeruginosa commonly found in the lungs of patients with cystic fibrosis (CF). It is known that phages and antibiotics can potentially show synergistic antimicrobial effect on bacterial killing. In the present study, we investigated synergistic antimicrobial effect of phage PEV20 with five different antibiotics against three P. aeruginosa strains isolated from sputum of CF patients. The antibiotics included ciprofloxacin, tobramycin, colistin, aztreonam and amikacin, which are approved by U.S Food and Drug Administration (FDA) for inhaled administration. Phage and antibiotic synergy was determined by assessing bacterial killing performing time-kill studies. Among the different phage-antibiotic combinations, PEV20 and ciprofloxacin exhibited the most synergistic effect. Two phage-ciprofloxacin combinations, containing 1/4 and 1/2 of the minimum inhibitory concentration (MIC) of ciprofloxacin against P. aeruginosa strains FADD1-PA001 (A) and JIP865, respectively were aerosolized using both air-jet and vibrating mesh nebulizers and the synergistic antibacterial activity was maintained after nebulization. Air-jet nebulizer generated droplets with smaller volume median diameters (3.6-3.7 µm) and slightly larger span (2.3-2.4) than vibrating mesh nebulizers (5.1-5.3 µm; 2.1-2.2), achieving a higher fine particle fraction (FPF) of 70%. In conclusion, nebulized phage PEV20 and ciprofloxacin combination shows promising antimicrobial and aerosol characteristics for potential treatment of respiratory tract infections caused by drug-resistant P. aeruginosa.

Keywords: Antibiotics; Bacteriophage; Ciprofloxacin; Cystic fibrosis; Inhalation; Nebulizer; Phage therapy; Pseudomonas aeruginosa; Respiratory tract infection.

Copyright © 2018 Elsevier B.V. All rights reserved.

Lin, Yu
Chang, Rachel Yoon Kyung
Britton, Warwick J.
Morales, Sandra
Kutter, Elizabeth
Chan, Hak-Kim
Last Modified: 03 Jan 2021 22:59

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