665. Clinical and Financial Impact of Next Generation Sequencing (NGS) in addition to Conventional Microbiology Testing in our Urban Referral Health Center

Abstract Background Clinical microbiology traditionally relies on culture methodology and serological testing, that have inherent limitations. Newer diagnostic techniques such as Next Generation Sequencing (NGS) have shown promise to improve microbial identification. In select scenarios, we send clinical specimens to reference laboratories for NGS testing in addition to current standard of care (SOC) diagnostics. We wanted to determine how this diagnostic approach has impacted patient care. We also wanted to review the financial burden through cost-benefit analysis for these ‘send-out’ tests. Methods We performed a retrospective chart review of all cases over a 3-year period in which NGS was submitted. Data, including demographics, comorbidities, antimicrobial use, and diagnosis (by SOC and NGS) were gathered. We delineated how often there was concordance or discordance between SOC and NGS. We also obtained information on financial cost (direct and indirect) and turnaround time (TAT) for NGS results. Results A total of 33 clinical specimens from 25 patients were sent for NGS. The majority of specimens comprised joint tissue/fluid, organ tissue and CSF. Concordance occurred between SOC and NGS testing in 75.8% (25/33) of samples; of those, 88% excluded infection. NGS identified a pathogen in 20% (5/25) patients in which concomitant SOC testing was negative. A subsequent change in antimicrobial management occurred in 16% (4/25) of patients. The mean TAT was 14 days and average cost per specimen was &821.52 (range: &573-&1590). Table 1. Pathogens identified by NGS with negative traditional microbiological test results Figure 1. Distribution of specimen site (in %) sent for NGS Conclusion NGS can provide additional diagnostic sensitivity in infectious diseases, which at our institution identified a new pathogen in 20% and a resultant treatment change in 16% of our patients. This testing may also allow physicians to reaffirm the absence of an infection diagnosis. A larger NGS testing population may reveal more significant benefits. While the attributable cost of NGS was substantial, it should be measured against the costs of administration of unnecessary antibiotics, inaccurate diagnosis, and adverse patient outcomes that may result from SOC testing alone. Considering its financial cost and extended TAT, in-house NGS testing may be warranted to facilitate a higher volume of testing. Disclosures All Authors: No reported disclosures

Background. Metagenomic next-generation sequencing (mNGS) of plasma cellfree 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 Background. Clinical microbiology traditionally relies on culture methodology and serological testing, that have inherent limitations. Newer diagnostic techniques such as Next Generation Sequencing (NGS) have shown promise to improve microbial identification. In select scenarios, we send clinical specimens to reference laboratories for NGS testing in addition to current standard of care (SOC) diagnostics. We wanted to determine how this diagnostic approach has impacted patient care. We also wanted to review the financial burden through cost-benefit analysis for these 'send-out' tests.

Clinical and Financial Impact of Next Generation Sequencing (NGS) in addition to Conventional Microbiology Testing in our Urban Referral Health Center
Methods. We performed a retrospective chart review of all cases over a 3-year period in which NGS was submitted. Data, including demographics, comorbidities, antimicrobial use, and diagnosis (by SOC and NGS) were gathered. We delineated how often there was concordance or discordance between SOC and NGS. We also obtained information on financial cost (direct and indirect) and turnaround time (TAT) for NGS results.
Results. A total of 33 clinical specimens from 25 patients were sent for NGS. The majority of specimens comprised joint tissue/fluid, organ tissue and CSF.
Concordance occurred between SOC and NGS testing in 75.8% (25/33) of samples; of those, 88% excluded infection. NGS identified a pathogen in 20% (5/25) patients in which concomitant SOC testing was negative. A subsequent change in antimicrobial management occurred in 16% (4/25) of patients. The mean TAT was 14 days and average cost per specimen was $821.52 (range: $573-$1590).  Figure 1. Distribution of specimen site (in %) sent for NGS Conclusion. NGS can provide additional diagnostic sensitivity in infectious diseases, which at our institution identified a new pathogen in 20% and a resultant treatment change in 16% of our patients. This testing may also allow physicians to reaffirm the absence of an infection diagnosis. A larger NGS testing population may reveal more significant benefits. While the attributable cost of NGS was substantial, it should be measured against the costs of administration of unnecessary antibiotics, inaccurate diagnosis, and adverse patient outcomes that may result from SOC testing alone. Considering its financial cost and extended TAT, in-house NGS testing may be warranted to facilitate a higher volume of testing.  Background. The global spread of methicillin-resistant Staphylococcus aureus (MRSA) is associated with distinct genetic lineages that predominate in specific geographical regions. Available evidence suggests the Chilean-Cordobes clone (ChC), an ST5-SCCmecI lineage, has largely predominated in Chilean hospitals since its first description in the late 1990's. Although the circulation of other MRSA lineages, including community-associated clones, has been well documented, the dynamics of clonal replacement over time has not been explored. Therefore, we aimed to study the molecular epidemiology and dynamics of clonal replacement using a large collection of clinical MRSA strains recovered from Chile during the last two decades.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in
Methods. We used whole-genome sequencing (WGS) and core-based phylogenomic analysis to identify genetic lineages and explore their relationship in 798 MRSA isolates obtained between 1999-2018 from two tertiary-care Chilean hospitals.