Metagenomic Next-generation Sequencing of Cerebrospinal Fluid: First-year Experience at a Tertiary Referral Hospital
Sergio Alvarez Mulett, Sofia Molina Garcia, Omar Abu Saleh, Matthew J. Wolf, Amanda A Rodning, Nancy L. Wengenack, Andrew P. Norgan, Robin Patel
Abstract
BACKGROUND: Central nervous system (CNS) infections are significant causes of morbidity and mortality, especially when diagnosis is delayed. Traditional cerebrospinal fluid diagnostic methods for CNS infections have limited sensitivity. Metagenomic next-generation sequencing of cerebrospinal fluid (MSCSF) is a newer diagnostic tool capable of detecting a broad range of pathogens in a single assay. METHODS: This retrospective cohort study evaluated the first-year experience with MSCSF at Mayo Clinic. A total of 422 tests performed during calendar year 2024 on adult patients at Mayo Clinic facilities and those tested through Mayo Clinic Laboratories were analyzed, with a subcohort analysis of the 210 Mayo Clinic patients performed to define patient characteristics associated with positive results and clinical outcomes. RESULTS: The sensitivity of MSCSF for detecting neuroinfection in the subcohort was 64%, with 43% of confirmed neuroinfections diagnosed by MSCSF only. Subjects who were immunosuppressed (odds ratio [OR]: 3.5, P = .008) and those with a high pretest probability of CNS infection (OR: 20.1, P < .001) were more likely to have positive results. Also, those who tested positive were more likely to die within the ensuing 30 days than those who tested negative (OR: 5.2, P = .001). CONCLUSIONS: MSCSF can be a valuable tool for diagnosing CNS infection but should not be used indiscriminately. It appears to be most beneficial when there is a high clinical suspicion of CNS infection and conventional diagnostics, and available molecular tests, yield negative results. Its integration into clinical practice should be guided by diagnostic stewardship to maximize cost-effectiveness and clinical utility.