Abstract
Aspergillus fumigatus endocarditis is a rare but severe infection associated with high mortality, typically affecting immunocompromised individuals. Diagnosing fungal endocarditis can be challenging due to the often negative blood cultures and nonspecific symptoms. We present a case of Aspergillus fumigatus infective endocarditis in a 59-year-old immunocompetent man with no typical risk factors, diagnosed with the assistance of metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius test). The patient presented with ocular symptoms and was found to have a heart murmur and a hypodense liver lesion, leading to suspicion of infective endocarditis. Blood cultures failed to reveal a pathogen, but elevated fungal biomarkers and the Karius test supported Aspergillus fumigatus as the causal agent. The patient received antifungal therapy with voriconazole and liposomal amphotericin B followed by surgical intervention for mitral valve replacement. The case exemplifies the difficulty in diagnosing Aspergillus endocarditis, as blood cultures are often negative and histological confirmation may be delayed. Molecular diagnostics, such as metagenomic microbial plasma cell-free DNA next-generation sequencing assay, significantly enhance pathogen detection in culture-negative cases. However, although treatment with antifungal therapy and surgery can improve outcomes, the high mortality associated with Aspergillus endocarditis remains a critical concern, highlighting the need for further research and advancements in both diagnostic and therapeutic approaches.