664. Clinical Impact of Cell-Free DNA Metagenomics in Diagnosing Infectious Diseases in Pediatrics: A Single-Center Experience

Background Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA has significant potential to improve infectious diseases diagnostics through unbiased detection of pathogens. However, the optimal patient population or clinical condition for this testing has not been determined. Methods We performed a retrospective review of all orders for plasma cell-free DNA mNGS using the Karius test (Karius, Redwood City, CA) from The Children’s Hospital of Philadelphia from 7/1/19-4/30/21. Chart review then determined if the test had a positive, negative, or no clinical impact. Results 25 mNGS tests were ordered on 24 unique patients. The majority of tests were ordered on immunocompromised patients (Table 1). Most mNGS tests were ordered after completion of routine microbiological testing (17/25, 71%). Three tests were not completed as ordered. Most completed tests (18/22, 82%) had no impact on clinical care as they confirmed the known diagnosis or were not acted upon (Figure 1). mNGS testing had a positive impact in 2 cases. For one patient with congenital heart disease presented with persistent fever and concern for endocarditis despite negative infectious workup, a negative mNGS result allowed for continued monitoring without therapy. Another patient with a lymphatics disorder had mNGS performed due to persistent clinical instability; testing was positive for Candida parapsilosis, allowing for early initiation of antifungal therapy. However, test results had a negative clinical impact in 2 other patients. In a patient with congenital heart disease and fever, identification of two organisms led to prolonged antibiotic therapy for endocarditis without resolution of symptoms. In a patient with leukemia, report of a dematiaceous mold led to further diagnostic testing, including a lumbar puncture, as well as treatment with antifungal therapy despite no clear diagnosis. Table 1 Conclusion In this study, the majority of plasma cell-free mNGS tests had no impact on clinical care. mNGS testing did positively impact care in 2 patients, but did had a negative impact on care in 2 instances, leading to further testing and unnecessary treatment. Further investigation is needed to determine the ideal population or clinical condition for testing and the ideal time of sending plasma cell-free mNGS tests. Disclosures All Authors: No reported disclosures