Improved pathogen identification in sepsis or septic shock by clinical metagenomic sequencing
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Objectives.
Despite limited sensitivity and specificity, blood cultures (BCs) still represent the gold standard of diagnostic care in septic patients. We aimed to overcome current diagnostic limitations by unbiased next-generation sequencing (NGS) of circulating microbial cell-free DNA (mcfDNA) in plasma samples.
Methods.
We performed a prospective, observational, non-interventional, multicenter study ( Next GeneSiS-Trial ) to compare positivity rates for NGS-based identification of causative pathogens with BCs in patients suffering from sepsis or septic shock. An independent expert panel (n=3) retrospectively evaluated the plausibility of NGS-based findings and the potential for anti-infective treatment adaptations based on NGS results.
Results.
The positivity rate of NGS-based diagnostics (NGS+) for 491 septic patients was 70.5% compared to positive BCs (BC+) with 19.4% within the first three days after sepsis onset. NGS+ results were evaluated as plausible in 98.6% of cases by the expert panel. Based on the expertś recommendations, additional knowledge of NGS-based pathogen findings would have resulted in anti-infective treatment adaptations in 32.6% of all patients. Potentially inadequately treated NGS+/blood culture negative (BC-) patients showed worse outcomes.
Conclusion.
The integration of NGS-based pathogen diagnostics in sepsis has the potential to improve patientś outcomes as compared to a treatment strategy based on standard-of-care microbiological diagnostics alone.
