Synergy of ultrasound microbubbles and vancomycin against Staphylococcus epidermidis biofilm

OBJECTIVES: Device-associated biofilm infections primarily caused by Staphylococcus epidermidis are difficult to treat effectively with conventional antibiotics. The aim of this study was to investigate the anti-biofilm effect of ultrasound-mediated microbubbles combined with vancomycin and to explore underlying mechanisms. METHODS: Twenty-four hour S. epidermidis biofilms were established in OptiCell(TM) chambers to facilitate ultrasound exposure. Microbubbles were prepared and diluted to concentrations of 1% and 4% (v/v). Ultrasound was applied for 5 min at 300 kHz and 0.5 W/cm(2), with a 50% duty cycle. Vancomycin at the peak serum concentration of 32 mg/L was used on preformed biofilms for 24 h. Antibiotic susceptibility tests were conducted on biofilms to confirm the synergy between ultrasound and vancomycin. Biofilms exposed to ultrasound-mediated microbubbles combined with vancomycin were subjected to plate counting and microscopic examinations. A vancomycin penetration test was also performed. RESULTS: Ultrasound and ultrasound-mediated microbubbles both enhanced biofilm susceptibility to vancomycin. Ultrasound-mediated microbubbles without vancomycin could exert a bactericidal effect on biofilms. A bubble dose-dependent bioeffect was also observed. In the presence of vancomycin, biofilms exposed to ultrasound-mediated microbubbles exhibited significantly more micropores and more reduction in biofilm thickness than other treatment groups (P<0.05). The transportation of vancomycin through S. epidermidis biofilms was significantly enhanced by ultrasound, and microbubbles could further increase biofilm permeability to vancomycin. CONCLUSIONS: Ultrasound-mediated microbubbles may provide an efficient and non-invasive alternative to treat device-related biofilm infections. Future research is needed to optimize ultrasound parameters and microbubble concentrations so that this technology can be both effectively and safely applied in clinical practice.