Abstract
BACKGROUND: Infectious diseases of the spine (IDS) cause structural destruction and abscess formation, requiring precise early diagnosis. While conventional culture methods show limited sensitivity and slow turnaround, metagenomic next-generation sequencing (mNGS) offers a promising alternative with its broader pathogen spectrum, rapid turnaround time, high detection rate, and sensitivity, showing significant advantages in the diagnosis of IDS. OBJECTIVES: This systematic review aims to synthesize the current evidence on the advantages and clinical utility of mNGS in diagnosing and managing IDS, focusing on pyogenic and granulomatous spinal infections. DESIGN: The systematic review conducted in accordance with PRISMA guidelines. DATA SOURCES AND METHODS: A comprehensive literature search was performed across nine electronic databases (including PubMed, Web of Science, and Embase) from 2010 to April 2025. Studies reporting on mNGS for pathogen detection in patients with suspected or confirmed spinal infections were included. The quality of included observational studies was assessed using the STROBE checklist. Data on detection spectrum, rate, sensitivity, turnaround time, and clinical impact were extracted and synthesized narratively due to high heterogeneity. RESULTS: Twenty-nine studies (25 retrospective studies and 4 case reports) from China were included. mNGS demonstrated a significantly broader detection spectrum, identifying common pathogens (e.g., Staphylococcus aureus, Mycobacterium tuberculosis) as well as rare and fastidious organisms that were missed by conventional methods. The pooled detection rate of mNGS (36.8%-95.5%) was consistently and significantly higher than that of culture (5.9%-59.2%). mNGS also showed superior sensitivity (39%-94.7%) compared to culture. The average turnaround time for mNGS (29-53 h) was substantially faster than for culture (2-10 days). mNGS-guided therapy was associated with improved clinical outcomes, including significant reductions in inflammatory markers. CONCLUSION: mNGS represents a powerful diagnostic tool for IDS, offering broader detection spectrum, higher detection rate, faster turnaround time, and greater sensitivity compared to conventional methods. This enables more targeted antimicrobial therapy and improves clinical management. Challenges including high costs and difficulty in distinguishing colonization from infection remain. Future efforts should focus on technical optimization, workflow automation, protocol standardization, and outcome validation in larger prospective studies. TRIAL REGISTRATION: CRD420251170912.