Not only have SAW been shown to reduce CAUTI development and increase antibiotic efficacy, but there has now been the first report of SAW affecting cell signalling via integrins.
A fibrin gel system was used to imitate both human and murine tissue-like environments, in which SAW, mediated by T-cell CD18 β2 integrins, were able to enhance the recruitment of neutrophils via chemotaxis to the infection site in response to a chemoattractant in both species. This lead to increased bacterial killing by neutrophils in S. epidermis, both within the biofilm and in the planktonic state. The exact bactericidal mechanism is still to be clarified but it is strongly suggested that the SAW either directly prevent bacterial growth within biofilms, that they complement and increase neutrophil cytolytic activity, or both.
The CD18 integrins are thought to have a role in increased bacterial killing following SAW treatment, by acting as a mechanoreceptor for the sound waves. This was highlighted in CD18 knockout mice, as their neutrophils were incapable of increasing bactericidal activity following SAW treatment, suggesting CD18 sensitivity to low-frequency ultrasound. SAW were able to increase bacterial cell death by 11% in 10-day biofilms at the P<0.05 degree of accuracy, and by 15% when repetitive bursts of SAW were administered during days 3-10. There was a 30% increase in CFU of S. epidermis killed at the P<0.001 degree of accuracy after just 90 minutes, to almost 100% of the 105 CFU being eliminated. It is not suggested that SAW increases phagocytosis or hydrogen peroxide production, but it is implied that it is the concentration of neutrophils rather than the effector to target cell ratio that governs neutrophil bactericidal activity. This occurs by aiding neutrophil chemotaxis through fibrin gels and therefore potentially in vivo. We can conclude that bacterial killing resulting in the elimination of infection is a consequence of processes increasing the capacity to meet and surpass the critical concentration of neutrophils in the body.