Abstract: A method for applying ultrasound to activate a cavitation enhancing agent in the presence of a therapeutic compound and a microbial biofilm is provided. The ultrasound energy causes the cavitation enhancing agent to cavitate in the ultrasound field. The cavitation of the resultant bubble causes fluid streaming and shear forces at and near the biofilm, causing enhanced penetration of the therapeutic compound into the biofilm, and resulting in improved efficacy of the therapeutic compound against the biofilm. The method further includes cavitation enhancing agents which can be loaded with oxygen gas or combined with microbubbles which carry oxygen gas, which further potentiate antibiotic efficacy against the biofilm.