Ultrasound Microbubbles Enhance the Activity of Vancomycin Against Staphylococcus epidermidis Biofilms In Vivo.

Abstract

Staphylococcus epidermidis is the predominant pathogen of device-associated infections. By forming biofilms on the device surface, S epidermidis has substantial resistance to antibiotics and is difficult to eradicate. This study aimed to explore the synergistic effect of ultrasound (US)-mediated microbubbles combined with vancomycin on S epidermidis biofilms in a rabbit model. Two polytetrafluoroethene catheters with preformed S epidermidis biofilms were implanted subcutaneously in a rabbit, one on either side of the spine. Animals were randomized into different treatment groups, with each rabbit acting as its own control and treatment. Ultrasound was applied from 24 to 72 hours after surgery 2 times a day. The parameters were 300 kHz and 0.5 W/cm2 in a 50% duty cycle, with or without microbubbles injected subcutaneously into the implantation site. After treatments, animals were euthanized, and implants were removed for a scanning electron microscopic examination and bacterial counting. The hearts, kidneys, livers, and subcutaneous tissues were sent for histopathologic examinations. Ultrasound + microbubbles increased the bactericidal action of vancomycin by decreasing biofilm viability from a mean ± SD of 6.44 ± 0.03 log10 colony-forming units per catheter in the control group to 3.49 ± 0.02 log10 colony-forming units per catheter in US + microbubble + vancomycin group (P < .001). The antibacterial effect of US + microbubbles + vancomycin was more pronounced than that of US + vancomycin (P < .001). Under scanning electron microscopy, biofilms exposed to US + microbubbles + vancomycin showed a greater reduction in thickness and bacterial density than other treatments. Histopathologic examinations showed no abnormalities in organs and skins. Ultrasound microbubbles enhanced the antibacterial effect of vancomycin against S epidermidis biofilms in vivo without exerting obvious harms to the animals.