LAUSR

Next-generation sequencing of microbial cell-free DNA (NGS cfDNA) testing has the potential to quickly diagnose multiple pathogen types. Negative predictive value of NGS cfDNA is not well characterized, but this test has been described as helpful in excluding infection diagnosis. This is a retrospective chart review study of 93 consecutive patients with first-time NGS cfDNA testing at a freestanding children’s hospital. Case results and exclusion are in figure 1. Each case was manually reviewed and then adjudicated as useful or not useful to the plan of care by two providers for agreement. Demographics, health history, diagnostics, and treatments were reviewed. Test results were considered useful if the NGS cfDNA test identified the causal pathogen and resulted before conventional testing, or if the test was actionable to help exclude infection. Figure 1.Case inclusion and overall categorization NGS cfDNA testing identified a pathogen responsible for illness exclusively, or before conventional testing in 15 cases (16%). In 67% (10) of these cases the patient had underlying oncology or congenital cardiac disease. In 11 cases, NGS cfDNA testing was used to change antibiotics (new antibiotic started in 7 cases; changed or deescalated in 2 cases; stopped in 2 cases). NGS cfDNA was used in 24 cases (26%) to help exclude infection as a diagnosis (5 positive for low level pathogens; 19 negative). In 5 cases, the NGS cfDNA test was negative, but conventional testing identified causative pathogens, which are detectable in this test. Of these, 3 were identified in cerebrospinal fluid and not in blood. Figures 2 and 3 describe NGS cfDNA findings. Figure 2:(2A) Demographics (2B) Underlying diagnosis and % positive and usefulFigure 3:Clinical utility of positive and negative tests. NGS cfDNA testing identified pathogens quickly and correctly in 16% of cases. The test was more often diagnostic in cases with underlying cardiac or oncology diagnosis, rather than in previously healthy patients. It was considered useful for its negative predictive value. However, in 5% of cases, the diagnosis was missed by NGS cfDNA testing. NGS cfDNA testing can provide valuable information regarding diagnosis. We caution against using this test as a single evaluative measure to exclude infection, particularly in cases where disease is suspected outside the bloodstream. All Authors: No reported disclosures.