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Abstract Background Standard microbiological testing (MT) fails to identify a pathogen in most chemotherapy recipients with febrile neutropenia (FN), who therefore receive prolonged empiric courses of broad-spectrum antimicrobials (AM). We evaluated the ability of the Karius next-generation sequencing plasma test (KT) to identify infectious etiologies of NF and its impact on AM management. Methods This prospective, observational study enrolled 57 patients with ≤500 neutrophils/mm3. Samples were collected within 24 hours of fever onset (T0) and every 2–3 days. Cell-free plasma DNA was prepared and sequenced in a CLIA/CAP laboratory, human reads excluded, and remaining sequences aligned to a curated pathogen database that includes bacteria, viruses, fungi and parasites. Positive agreement (PA) was defined as KT identification of ≥1 isolate also seen by blood culture (BC). Discordant results were adjudicated by 3 infectious disease specialists as: Definite: KT identified ≥1 organism also seen by MT± 7 days of enrollment; Probable: KT result was a likely cause of NF compatible with clinical diagnosis; Possible: KT result was consistent with an infection but not a common cause of NF. Results 56 results (55 subjects) with valid KT and BC results were analyzed. Compared with BC, KT had a PA of 90% (9/10) and negative agreement of 31% (14/45). KT identified >1 organism in 61% (25/41) of the cases. Definite (13), Probable (24) and Possible (4) cases were classified as True Positives. Using clinical adjudication, KT had a sensitivity of 98% (41/42) and specificity of 100% (14/14). The committee would have changed AM therapy 68% (27/40) of the time, had the KT results been available in real-time (~T52–100h). In 8/19 cases (42%) vancomycin would have been discontinued; in 6/27 cases (22%) and in 5/27 cases (19%), anaerobic coverage or antivirals would have been added earlier. Serial analysis of a Pneumocystis jirovecii infection indicated that earlier diagnosis and treatment may have prevented morbidity and eventual ICU transfer. Conclusion The absence of infectious etiology in NF often leads to broad AM therapy or delay of targeted treatment. Given its sensitivity and ability to detect a breadth of pathogens, the KT can provide useful data for diagnosis and management of NF and may allow for optimization of AM therapy. Disclosures H. Seng, Karius, Inc.: Employee, Salary. R. Aquino, Karius, Inc.: Employee, Salary. D. Hollemon, Karius: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. T. Blauwkamp, Karius, Inc.: Board Member, Employee and Shareholder, Salary. M. Kertesz, Karius Inc.: Board Member, Employee and Shareholder, Salary. L. Blair, Karius: Employee, Salary. S. Zompi, Karius, Inc.: Employee, Salary.

open forum infectious diseases

2294. Evaluation of the Karius Plasma Next-Generation Sequencing Cell-free Pathogen DNA Test to Determine the Etiology of Infection and Impact on Anti-Microbial Management in Patients with Severe Neutropenia and Fever