Antibiotics (Oct 2022)

The Combination of Low-Frequency Ultrasound and Antibiotics Improves the Killing of In Vitro <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> Biofilms

  • Lasse Kvich,
  • Mads H. Christensen,
  • Malgorzata K. Pierchala,
  • Konstantin Astafiev,
  • Rasmus Lou-Moeller,
  • Thomas Bjarnsholt

DOI
https://doi.org/10.3390/antibiotics11111494
Journal volume & issue
Vol. 11, no. 11
p. 1494

Abstract

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Due to an increase in underlying predisposing factors, chronic wounds have become an increasing burden on healthcare systems worldwide. Chronic infections often contain biofilm-forming bacteria, which are challenging to eradicate due to increased antibiotic tolerance; thus, new and improved therapeutic strategies are warranted. One such strategy is the combination of ultrasound and antibiotics. Therefore, this study aimed to investigate the combinatory effects of low-frequency (50 kHz) ultrasound delivered by specially designed ultrasound patches using flexible piezoelectric material, PiezoPaint™, in combination with antibiotics against biofilms with Staphylococcus aureus and Pseudomonas aeruginosa. The reduction in viable cells in S. aureus and P. aeruginosa biofilms was evaluated post-treatment with fusidic acid, clindamycin, ciprofloxacin, and colistin in combination with ultrasound treatment. Two-hour ultrasound treatment significantly increased the bactericidal effect of all four antibiotics, resulting in a 96–98% and 90–93% reduction in P. aeruginosa and S. aureus, respectively. In addition, an additive effect was observed when extending treatment to 4 h, resulting in >99% and 95–97% reduction in P. aeruginosa and S. aureus, respectively. These results contrasted the lack of effect observed when treating filter-biofilms with antibiotics alone. The combined effect of ultrasound and antibiotic treatment resulted in a synergistic effect, reducing the viability of the clinically relevant pathogens S. aureus and P. aeruginosa. The modularity of the specially designed patches intended for topical treatment holds promising applications as a supplement in chronic wound therapy. Further studies are warranted with clinically isolated strains and other clinically relevant antibiotics before proceeding to studies where safety and applicability are investigated.

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