Diagnostic Performance of Clinical Metagenomic Next-Generation Sequencing for Suspected Central Nervous System Infections in a Municipal Hospital: A Retrospective Study in China

Abstract

Purpose: Cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) has the potential to identify the majority of pathogens in a single test. Accurate pathogen identification is vital for central nervous system infection (CNSi). However, there are few related studies investigating in a municipal hospital.

Patients and methods: A total of 52 suspected CNSi patients were retrospectively recruited in Xinxiang central hospital between July 2019 and April 2023. The diagnostic performance of CSF mNGS, conventional microbiological tests (CMT), and the combination of CSF mNGS and CMT were evaluated by comparing to the final diagnosis.

Results: Among 52 suspected CNSi patients, 35 were diagnosed as CNSi. In comparison to the final diagnosis, the area under curves (AUC) for CSF CMT, CSF mNGS, and the combination of CMT and mNGS for the diagnosis of CNSi were 0.56 (95% CI 0.4-0.72), 0.74 (95% CI 0.61-0.84), and 0.76 (95% CI 0.63-0.88), respectively. The sensitivities were 11.43% (95% CI 4.54%-25.95%), 48.57% (95% CI 32.99%-64.43%), and 51.43% (95% CI 35.57%-67.01%), respectively. The accuracy was 40.38 (95% CI 27.01%-54.90%), 65.38% (95% CI 50.91%-78.03%), and 67.31% (95% CI 52.89%-79.67%), respectively. Furthermore, based on CSF mNGS results, seven patients confirmed initial treatment, two escalated, and one de-escalated. Additionally, we identified the optimal cutoff values as 1.75 U/L for CSF adenosine deaminase (ADA), 75.44 U/L for CSF protein, and 185 mmH₂O for CSF pressure, when these values were exceeded, CSF mNGS tended to yield positive results.

Conclusion: CSF mNGS showed superior diagnostic performance in CNSi and hence could serve as a complementary tool to CMT and conjunctively guide the precision therapy. Additionally, the values for CSF ADA, protein and pressure could assist in predicting mNGS positive result. With technical improvements for mNGS sample processing to increase throughput and reduce costs, clinicians may use mNGS more widely in municipal hospital laboratories.

Keywords: CMT; CNS infections; CSF; conventional microbiological tests; mNGS.

Figure 1

The flowchart of this study. (A) Samples screening and inclusion. (B) Workflow of mNGS.

Figure 2

The significant differences in clinical data between the CNSi and NCNSi groups. (A) Duration from initial symptoms to hospitalization. (B) Serum D-dimer. (C) CSF adenosine deaminase (ADA). Data are presented as a box plot overlaid by a dot plot with a line at the median. P values were calculated using the Wilcoxon rank sum test. *p value < 0.05.

Figure 3

The diagnostic performance of mNGS and pathogen spectrum in CNS infections. (A) CSF mNGS and CMT in CNSi. (B) Pathogen distribution in CNSi. (C) ROC curves of CSF mNGS, CMT, and the combination of mNGS and CMT in CNSi. P values were calculated using the Chi-square tests. **p value < 0.01; ***p value < 0.001.

Figure 4

The adjustment of initial antimicrobial treatment. (A) Adjustment of initial antibiotics in CNSi. (B) Adjustment of initial antibiotics in NCNSi.

Figure 5

The CSF clinical data related to the positive mNGS results. CSF ADA (A), CSF protein (B), and CSF pressure (C) were significantly different between mNGS-positive and mNGS-negative groups. The mNGS detection rate was significantly higher when CSF ADA ≥ 1.75 U/L (D), CSF protein ≥ 75.44 U/L (E), and CSF pressure ≥ 185 mmH₂O (F). (A–C) Data are presented as a box plot overlaid by a dot plot with a line at the median, and P values were calculated using the Wilcoxon rank sum test. *p value < 0.05; **p value < 0.01.