Exebacase in Addition to Standard-of-Care Antibiotics for <i>Staphylococcus aureus</i> Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT)

Exebacase + antibiotics failed to improve clinical response at day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics-alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis. Clinical Trials Registration.NCT04160468.