Metagenomic next-generation sequencing in blood culture-negative endocarditis: a structured review with illustrative...

Infective endocarditis is a life-threatening cardiovascular infection with high morbidity and mortality. Identification of the causative microbial pathogen is essential for targeted antimicrobial treatment. Blood culture-negative endocarditis accounts for up to 30% of the cases and supplementary diagnostics (antigen, serology, histopathology, PCR, 16 S/18S) are unable to detect all pathogens. Recent sequencing-based diagnostics, including metagenomic next-generation sequencing (mNGS), have been incorporated as adjunctive tools in the 2023 Duke-ISCVID criteria.

This is a structured literature review with illustrative pooled estimates retrieved from PubMed and Google Scholar using searches for infective endocarditis including BCNE cases and sequencing methods.

The database searches identified 12 clinical studies with 794 patients, 10 prospective and two retrospective studies; no randomised controlled trials. Illustrative pooled estimates were calculated using random-effects meta-analyses of proportions and presented in forest plots; mNGS microbial diagnostic yield 0.87 (0.83-0.89), mNGS valve tissue pooled diagnostic yield 0.92 (0.80-0.97), blood culture diagnostic yield 0.43 (0.28-0.58) and valve tissue diagnostic yield 0.23 (0.12-0.39). Relative diagnostic yield, based on ratios of pooled proportions, showed a 2-fold lower yield for blood culture vs. mNGS and a 4-fold lower yield for valve tissue culture vs. mNGS.

mNGS is increasingly being implemented in routine infective endocarditis diagnostics and has consistently demonstrated high diagnostic yield across heterogeneous studies, particularly in valve tissue compared with blood and valve tissue culture. Consensus on diagnostic algorithms, standardised mNGS testing, and randomised controlled trials are needed to further define the role of mNGS in BCNE.