A fresh shine on cystic fibrosis inhalation therapy: Antimicrobial synergy of polymyxin B in combination with silver nanoparticles

Raad Jasim, Elena K. Schneider, Meiling Han, Mohammad A.K. Azad, Maytham Hussein, Cameron Nowell, Mark A. Baker, Jiping Wang, Jian Li, Tony Velkov

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

This in vitro study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with 2 nm silver nanoparticles (NPs) against Gram-negative pathogens commonly isolated from the cystic fibrosis (CF) lung. The in vitro synergistic activity of polymyxin B with silver NPs was assessed using the checkerboard assay against polymyxinsusceptible and polymyxin-resistant Pseudomonas aeruginosa isolates from the lungs of CF patients. The combination was also examined against the Gram-negative species Haemophilus influenzae, Burkholderia cepacia, Burkholderia pseudomallei, Stenotrophomonas maltophilia, Klebsiella pneumoniae and Acinetobacter baumannii that are less common in the CF lung. The killing kinetics of the polymyxin B-silver NPs combinations was assessed against P. aeruginosa by static time-kill assays over 24 h. Polymyxin B and silver NPs alone were not active against polymyxin-resistant (MIC ≥ 4 mg/L) P. aeruginosa. Whereas, the combination of a clinically-relevant concentration of polymyxin B (2 mg/L) with silver NPs (4 mg/L) successfully inhibited the growth of polymyxin-resistant P. aeruginosa isolates from CF patients as demonstrated by ≥ 2 log10 decrease in bacterial count (CFU/mL) after 24 h. Treatment of P. aeruginosa cells with the combination induced cytosolic GFP release and an increase of cellular reactive oxygen species. In the nitrocefin assay, the combination displayed a membrane permeabilizing activity superior to each of the drugs alone. The combination of polymyxin B and silver NPs displays excellent synergistic activity against highly polymyxin-resistant P. aeruginosa and is potentially of considerable clinical utility for the treatment of problematic CF lung infections.

Original languageEnglish
Pages (from-to)447-457
Number of pages11
JournalJournal of Biomedical Nanotechnology
Volume13
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • Antibiotic combination
  • Cystic fibrosis
  • Nanoparticles
  • Polymyxin
  • Silver

Cite this