Abstract Background Culture-negative infective endocarditis (IE) presents significant diagnostic and therapeutic challenges, especially in patients with systemic embolic complications. Case Summary A middle-aged man with a history of intravenous drug use (IVDU) presented with fever, new apical systolic murmur, and widespread embolic phenomena affecting brain, spleen, kidneys, and lower limb. Transthoracic echocardiography (TTE) revealed a large posterior mitral leaflet vegetation with moderate-severe mitral regurgitation (MR). Blood and tissue cultures were negative. Next-generation sequencing (NGS) of an aspirated calf muscle abscess identified Rothia dentocariosa. Despite prolonged antimicrobial therapy and multidisciplinary care, persistent vegetations and high embolic risk prompted mitral valve replacement after interval stabilization of intracranial hemorrhages. He recovered without recurrent emboli and with stable prosthetic valve function. Conclusion Advanced molecular diagnostics like NGS can be crucial for identifying pathogens in culture-negative endocarditis. Multidisciplinary collaboration and individualized surgical timing are important for achieving optimal outcomes in complex cases with neurological complications.
H. Lam (2026) studied this question.