Sonobactericide: An ultrasound-mediated adjunct treatment for bacterial infective endocarditis—In vitro proof-of-principle

Abstract

Infective endocarditis (IE) is a bacterial infection of the surfaces within the heart, associated with high morbidity and mortality rates. The predominant bacteria causing IE are Staphylococci, which can bind to existing thrombi on heart valves and generate vegetations (biofilms). In this in vitro study, we test a novel strategy called sonobactericide to treat IE using ultrasound and ultrasound contrast agents, in combination with an antibiotic and a thrombolytic. We simulated IE vegetations using human whole-blood clots infected with Staphylococcus aureus. Histology and live-cell imaging revealed a biofilm layer of fibrin-embedded living Staphylococci. Infected clots were treated under flow for 30 min and degradation was assessed by time-lapse microscopy imaging. Clots were exposed to human plasma flow either alone or with different combinations of therapeutics: oxacillin (172 μg/mL), recombinant tissue plasminogen activator (rt-PA; 3.15 μg/mL), intermittent (50 s on, 30 s off) continuous-wave ultrasound (120 kHz, 0.44 MPa peak-to-peak pressure), and Definity (2 μl/ml). Infected clots exposed to the combination of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 ± 1.7% clot width loss, which was greater than the other treatment arms. These results demonstrate that sonobactericide may have potential as an adjunct therapy for IE.