- Title
- A fresh shine on cystic fibrosis inhalation therapy: antimicrobial synergy of polymyxin B in combination with silver nanoparticles
- Creator
- Jasim, Raad; Schneider, Elena K.; Han, Meiling; Azad, Mohammad A. K.; Hussein, Maytham; Nowell, Cameron; Baker, Mark A.; Wang, Jiping; Li, Jian; Velkov, Tony
- Relation
- Journal of Biomedical Nanotechnology Vol. 13, Issue 4, p. 447-457
- Publisher Link
- http://dx.doi.org/10.1166/jbn.2017.2355
- Publisher
- American Scientific Publishers
- Resource Type
- journal article
- Date
- 2017
- Description
- 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 polymyxin-susceptible 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.
- Subject
- silver; nanoparticles; cystic fibrosis; antibiotic combination; polymyxin
- Identifier
- http://hdl.handle.net/1959.13/1400976
- Identifier
- uon:34845
- Identifier
- ISSN:1550-7033
- Language
- eng
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