Diagnostic Benefit of Molecular Imaging in Patients Undergoing Heart Valve Surgery for Infective Endocarditis

(1) Background: The successful treatment of infective endocarditis (IE) relies on detecting causative pathogens to administer targeted antibiotic therapy. In addition to standard microbiological cultivation of pathogens from tissue obtained during heart valve surgery, the potential of molecular biological methods was evaluated. (2) Methods: A retrospective study was performed on heart valve tissue from 207 patients who underwent heart valve surgery for IE. FISHseq (fluorescence in situ hybridization combined with 16S rRNA gene PCR and sequencing) was performed in addition to conventional culture-based microbiological diagnostics. The diagnostic performance of FISHseq was compared with the conventional methods and evaluated in the clinical context. (3) Results: Overall, FISHseq provided a significantly higher rate of specific pathogen detection than conventional valve culture (68.1% vs. 33.3%, <i>p</i> < 0.001). By complementing the findings from blood culture and valve culture, FISHseq was able to provide a new microbiological diagnosis in 10% of cases, confirm the cultural findings in 24.2% of cases and provide greater diagnostic accuracy in 27.5% of cases. FISHseq could identify a pathogen in blood-culture-negative IE in 46.2% of cases, while valve culture provided only 13.5% positive results (<i>p</i> < 0.001). (4) Conclusions: This study demonstrates that using FISHseq as an additional molecular biological technique for diagnostics in IE adds substantial diagnostic value, with potential implications for the treatment of IE. It provides pathogen detection, especially in cases where conventional microbiological cultivation is negative or inconclusive.