236. The Comparative Utility Of Metagenomic Next-Generation Sequencing and Universal PCR for Pathogen Detection on Cerebrospinal Fluid: A Retrospective Analysis From a Tertiary Care Center

BACKGROUND: Many neurologic syndromes are underpinned by infectious etiologies that are difficult to diagnose. Broad-range, universal PCR (uPCR), and metagenomic next-generation sequencing (mNGS) are emerging molecular techniques that may allow for enhanced pathogen detection in challenging cases. To date, their comparative clinical utility for pathogen detection in cerebrospinal fluid (CSF) has not been described. METHODS: We searched the electronic medical record at University of California, San Francisco for all patients who had mNGS and uPCR results available from the same CSF specimen. Using all available clinical information, patients’ clinical episodes were categorized into one of four categories: (1) confirmed central nervous system (CNS) infection, (2) likely CNS infection, (3) confirmed/likely noninfectious etiology, (4) unknown etiology. We also determined whether mNGS and/or uPCR results changed clinical management. RESULTS: We identified 75 patients with 78 paired mNGS and uPCR results on CSF. 14/78 (17.9%) had a confirmed CNS infection underpinning their clinical presentation, 11 (14.1%) had a likely CNS infection, 33 (42.3%) had a likely noninfectious cause, and 20 (25.6%) had etiologies that could not be determined. Of the 14 patients with confirmed CNS infection, n = 4 (28.6%) were diagnosed by mNGS and n = 1 (7.1%) by uPCR (Table 1). Most diagnoses missed by mNGS and uPCR were made by CSF serology or from sites other than CSF. Overall, mNGS detected a pathogen in n = 10/78 (12.8%) cases, compared with n = 4/78 (5.1%) using uPCR (Table 2). Among those with a positive mNGS result, n = 6/10 represented a true or likely true positive result, while the remaining were likely contaminants. Of those with a positive uPCR result, n = 1/4 represented a true positive result, while n = 3/4 were likely contaminants. Clinical management was changed by the mNGS or uPCR result in two cases (Table 2). CONCLUSION: mNGS appears to have superior clinical utility to that of universal PCR for pathogen detection in CSF samples, in large part because of additional ability to detect DNA and RNA viruses. Further studies are required to determine the clinical contexts in which mNGS is likely to have maximal diagnostic yield and to better define the utility of uPCR for CNS infections. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.