Microbial Cell-Free DNA Sequencing as a Novel Diagnostic for Culture-Negative Gemella haemolysans Endocarditis.

backgroundInfective endocarditis (IE) is a known complication of repaired congenital heart disease. Blood culture-negative endocarditis (BCNE) remains a diagnostic challenge, often delaying pathogen-directed antimicrobial therapy. CASE SUMMARY: We report a 5-year-old girl with a repaired partial atrioventricular canal defect who presented with intracranial hemorrhage from a ruptured cerebral aneurysm. Transthoracic echocardiography revealed a mitral valve vegetation concerning for IE, although multiple blood cultures remained negative. Plasma microbial cell-free DNA (mcfDNA) sequencing subsequently identified Gemella haemolysans. She underwent emergent neurosurgical and endovascular intervention followed by targeted antimicrobial therapy, with subsequent neurological recovery. DISCUSSION: This case illustrates the utility of mcfDNA sequencing in the diagnosis of BCNE, particularly in the context of rare and fastidious organisms such as Gemella. Early diagnosis enables pathogen-directed treatment and highlights the importance of advanced molecular diagnostics in pediatric IE. TAKE-HOME MESSAGE: Plasma mcfDNA sequencing can facilitate diagnosis of BCNE, guiding targeted therapy.