New Perspectives for Prosthetic Valve Endocarditis: Impact of Molecular Imaging by FISHseq Diagnostics

Abstract Background The microbial etiology of prosthetic valve infective endocarditis (PVE) can be difficult to identify. Our aim was to investigate the benefit of molecular imaging technique fluorescence in situ hybridization (FISH) combined with 16S rRNA-gene polymerase chain reaction (PCR) and sequencing (FISHseq) for the analysis of infected prosthetic heart valves. Methods We retrospectively evaluated the diagnostic outcome of 113 prosthetic valves from 105 patients with suspected PVE, treated in 2003–2013 in the Department of Cardiac Surgery, Charité University Medicine Berlin. Each prosthetic valve underwent cultural diagnostics and was routinely examined by FISH combined with 16S rRNA gene PCR and sequencing. We compared classical microbiological culture outcomes (blood and valve cultures) with FISHseq results and evaluated the diagnostic impact of the molecular imaging technique. Results Conventional microbiological diagnostic alone turned out to be insufficient, as 67% of preoperative blood cultures were noninformative (negative, inconclusive, or not obtained) and 67% of valve cultures remained negative. FISHseq improved the conventional cultural diagnostic methods in PVE in 30% of the cases and increased diagnostic accuracy. Of the valve culture–negative PVE cases, FISHseq succeeded in identifying the causative pathogen in 35%. Conclusions FISHseq improves PVE diagnostics, complementing conventional cultural methods. In addition to species identification, FISH provides information about the severity of PVE and state of the pathogens (eg, stage of biofilm formation, activity, and localization on and within the prosthetic material). As a molecular imaging technique, FISHseq enables the unambiguous discrimination of skin flora as contaminant or infectious agent. Identification of the pathogen in prosthetic heart-valve endocarditis (PVE) is critical for diagnosis and therapy. Molecular diagnostics using FISHseq both directly visualizes and identifies the PVE pathogen. Thus, FISHseq delivered new diagnostic information in 30% of cases. Graphical Abstract