{Reference Type}: Journal Article {Title}: Blood Culture Negative Endocarditis: A Review of Laboratory Diagnostic Approaches. {Author}: Lin KP;Yeh TK;Chuang YC;Wang LA;Fu YC;Liu PY; {Journal}: Int J Gen Med {Volume}: 16 {Issue}: 0 {Year}: 2023 {Factor}: 2.145 {DOI}: 10.2147/IJGM.S393329 {Abstract}: Infective endocarditis is a potentially fatal condition, and identifying the pathogen is crucial to optimizing antibiotic treatment. While a blood culture takes time and may yield negative results, it remains the gold standard for diagnosis, blood culture-negative endocarditis, which accounts for up to 20% of infective endocarditis cases, poses a clinical challenge with increasing mortality. To better understand the etiology of blood culture-negative infective endocarditis, we reviewed non-culture-based strategies and compared the results. Serology tests work best in limited pathogens, such as Coxiella burnetii and Bartonella infections. Most of the pathogens identified by broad-range PCR tests are Streptococcus spp, Staphylococcus spp and Propionibacterium spp. adding specific real-time PCR assays to the systematic PCR testing of patients with blood culture-negative endocarditis will increase the efficiency of diagnosis. Recently, metagenomic next-generation sequencing has also shown promising results.