TARGET ENRICHED METAGENOMICS IN CEREBROSPINAL FLUID IN CENTRAL NERVOUS SYSTEM INFECTIONS.

OBJECTIVES: Metagenomic next-generation sequencing (mNGS) is a promising tool for identifying pathogens. Targeted enrichment may improve detection in samples with low pathogen loads. We evaluated targeted mNGS for the diagnosis of central nervous system infections. METHODS: We evaluated targeted mNGS using the Illumina Respiratory Pathogen ID/AMR Enrichment Panel Kit (RPIP) in CSF samples from 136 patients included in two prospective Dutch cohort studies. Patients had microbiologically confirmed CNS infections or a suspected CNS infection without identified pathogen. Conventional microbiological testing (culture and PCR) was used as the reference standard. RESULTS: Among 118 patients with a confirmed CNS infection (bacteria, n=78; viruses, n=33; fungi, n=7), targeted mNGS detected the expected pathogen in 70 patients (positive agreement 59%). In addition to expected detections, 71 unexpected pathogens were identified (71/141, 50% of all positive results). Among the 18 patients with a suspected CNS infection and negative conventional diagnostics, targeted mNGS identified a potential pathogen in 8 patients (44%), of which 7 (88%) were confirmed by qPCR. CONCLUSIONS: Targeted mNGS shows moderate agreement with conventional diagnostics and may aid pathogen detection in selected patients with negative routine testing. However, the high rate of unexpected detections and lack of standardized thresholds currently limit its clinical applicability.