From culture to metagenomics: A paradigm shift in diagnosing infective endocarditis.

Infective endocarditis (IE) is a severe disease that damages heart valves and can lead to major complications, including heart failure, embolic events, and stroke. It is the third most common fatal infection worldwide. This review examines the clinical burden of IE, its microbial causes, and the ongoing challenges in diagnosis. Particular attention is given to the limitations of traditional blood cultures, especially in detecting culture-negative and fastidious organisms, and to the emerging role of metagenomic approaches. A comprehensive review of the literature was conducted, focusing on diagnostic methods such as blood cultures, molecular assays, and metagenomic sequencing. The role of bacterial biofilms in treatment failure and antibiotic resistance was also explored. Metagenomics, especially cell-free metagenomic DNA (cf-mDNA), shows promise as a non-invasive diagnostic tool that can overcome culture-based limitations. However, standardized protocols and prospective studies are needed to validate its routine clinical application in IE diagnosis and management.