Blood Culture–Negative Infective Endocarditis Diagnosed via 16S rRNA Gene Amplicon Sequencing

Background: Infective endocarditis (IE) is typically diagnosed using the 2023 Duke-International Society for Cardiovascular Infectious Diseases criteria, which emphasize positive blood culture results. However, these criteria do not include genome sequencing. The 16S ribosomal ribonucleic acid (rRNA) gene sequencing shows promise for pathogen identification and early detection, particularly in blood culture–negative IE (BCNE). Case Summary: A 71-year-old man with recurrent fever and dyspnea was diagnosed with IE, causing severe aortic and mitral regurgitation. Although blood culture results were negative, 16S rRNA gene amplicon sequencing identified Streptococcus as the causative pathogen. Valve replacement surgery successfully resolved IE and heart failure. Discussion: Negative culture results were most likely due to prior antibiotic therapy. However, 16S rRNA gene amplicon sequencing revealed a high abundance of Streptococcus in the heart, blood, and saliva, demonstrating its diagnostic utility for BCNE. Take-Home Message: Integrating sequencing technology with bioinformatics advances the diagnosis of IE by enabling early, precise pathogen identification, particularly in BCNE cases.