Microbubble-mediated adjunct treatment for cardiovascular bacterial infections

Cardiovascular bacterial infections of tissue and indwelling devices are associated with high mortality rates. Infecting bacteria encase themselves in fibrin-based biofilms that hinder the immune system and antibiotics. In this in vitro study, we investigated sonobactericide to treat these biofilms using ultrasound and microbubbles, with and without a thrombolytic agent (rt-PA). Cardiovascular-mimicking biofilms were grown using human plasma inoculated with Staphylococcus aureus from an inner heart infection. Treatment consisted of ultrasound (2 MHz, 400 kPa, 100 cycles, every second for 30 s and 1 s continuous wave) every min for 10 min, either alone or with low-dose rt-PA (158 ng/ml), microbubbles, or rt-PA and microbubbles, and was assessed by time-lapse confocal microscopy. Ultrasound-activated microbubbles bent fibrin strands (≤5.2 μm), which returned to original positions (≤25.6 s), and dislodged bacteria from fibrin encasement. Ultrasound alone did not physically alter biofilms. Oscillating microbubbles with rt-PA present led to fibrin strand bending, with and without recovery and eventual breaking, and faster fibrin degradation liberating bacterial aggregates (322 ± 161 s) than rt-PA alone (518 ± 86 s; excluding ∼45 min from rt-PA exposure until degradation began). These results demonstrate that microbubble-induced effects could aid in the treatment of cardiovascular biofilm infections.