How Molecular Diagnostics Are Transforming Pathogen Detection When Cultures Are Negative

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Blood cultures fail to identify a pathogen in an estimated 2.5% to 31% of infective endocarditis cases, often because organisms are fastidious or intracellular.
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The 2023 Duke–International Society for Cardiovascular Infectious Diseases criteria added molecular methods to the major microbiological criteria for infective endocarditis.
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Plasma microbial cell-free DNA sequencing can detect pathogens without a prespecified hypothesis and remains positive longer after antibiotics than blood cultures.
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In a 141-patient suspected-endocarditis cohort, microbial cell-free DNA sequencing detected a pathogen in 60.6% of confirmed cases and was the sole positive test in one third of detections.
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Microbial cell-free DNA sequencing can yield clinically insignificant detections, provides no susceptibility data, and requires interpretation in clinical context.

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