Abstract
We report a fatal case of Legionella micdadei prosthetic valve endocarditis in a patient who was immunocompromised, characterised by an indolent outpatient course followed by rapid clinical deterioration into mixed shock secondary to valve dehiscence and sepsis. The diagnosis was made by plasma microbial cell-free DNA metagenomic next-generation sequencing (mcfDNA-mNGS) and confirmed by buffered charcoal yeast extract culture of valve tissue. This case underscores the diagnostic limitations of conventional methods in culture-negative endocarditis, the evolving role of mcfDNA-mNGS in culture-negative endocarditis, and the absence of current culture-negative endocarditis guidelines addressing timely diagnosis for patients who are at risk of rapid deterioration. In this Grand Round, we briefly review the state of diagnostics for culture-negative endocarditis and the particularities of Legionella endocarditis. We also propose a framework for deciding when to consider early metagenomic testing, balancing the potential strengths of this technology with its limitations and cost.