Microbiological Diagnostic Performance and Clinical Effect of Metagenomic Next-Generation Sequencing for the Detection of Immunocompromised Patients With Community-Acquired Pneumonia

Abstract

Objective: Community-acquired pneumonia (CAP) presents a significant public health concern, necessitating timely and precise diagnosis. Metagenomic next-generation sequencing (mNGS) has shown promise as a powerful tool for pathogen identification in infectious diseases. This study aimed to evaluate the diagnostic efficacy and clinical applicability of mNGS for immunocompromised patients with CAP compared to the culture method.

Methods: This study included 168 patients. We used both mNGS and conventional culture methods to identify the pathogen spectrum and evaluate diagnostic performance. Treatment regimens and clinical outcomes were meticulously documented.

Results: The sensitivity of mNGS was greater than that of the culture method across all samples (79.05% vs 16.03%; p < 0.001). mNGS identified pathogens missed by culture in 59.52% of patients and detected polymicrobial infections that were not detected by culture in 47.62% of patients. Streptococcus pneumoniae, Candida albicans, and Human herpesvirus 4 at classification level emerged as the predominant pathogens identified in CAP patients through mNGS. When examining the mNGS results between groups, the proportions of immunocompromised patients with bacterial (p < 0.001), fungal (p < 0.001), viral (p < 0.05), and mixed infections (p < 0.001) were all significantly higher than those in immunocompetent patients. Treatment adjustments guided by mNGS were observed in 73.21% of patients. Specifically, a beneficial clinical effect was observed in 50.60% (85/168) of patients, treatment confirmation in 22.62% (38/168) of patients, and no clinical benefit in 26.80% (45/168) of patients based on mNGS-guided antibiotic treatment adjustments.

Conclusion: These findings highlight the diagnostic performance of mNGS for identifying pathogens, particularly in immunocompromised patients vulnerable to infections, offering valuable insights for clinical decision-making.

Keywords: clinical effect; community-acquired pneumonia; diagnostic performance; immunocompromised; metagenomic next-generation sequencing.

Figure 1

Positive rate and agreement of BALF metagenomic next-generation sequencing (mNGS) compared to culture in 168 CAP patients. (A) The composition of sample types and positive sample distribution for culture detection. (B) Positive rate comparison for mNGS and culture methods. (C) Concordance analysis of pathogens detected via two methods. (D) The 80 patients with polymicrobial infections, including 30% patients with bacteria and fungi, 26% patients with bacteria and virus, 35% patients with multiple bacteria, 1% patient with fungi and virus, and 8% patients with three types pathogen infection.

Figure 2

The number of each microbiological pathogen detected by mNGS and culture method. Red bars indicate pathogens detected by mNGS only (culture-mNGS+); Green bars show each pathogen detected by culture only (culture+mNGS-); Blue bars indicate pathogens detected by both mNGS and culture (culture+mNGS+).

Figure 3

Differences and overlap in the pathogenic spectrum between immunocompromised patients and immunocompetent patients. The detection number of each microbe was calculated. Bacteria were the most detected, followed by viruses and fungi, special pathogens.

Figure 4

The comparison of microbiological pathogens between immunocompromised patients and immunocompetent patients and mNGS-guided antibiotic treatment adjustments in patients. (A) The positive rate difference of bacteria, fungi virus and mixed infection in immunocompromised patients compared to immunocompetent patients. *p value < 0.05; ***p value < 0.001. (B) The antibiotic treatment adjustment based on mNGS. (C) Clinical effect of mNGS on treatment in 168 patients with CAP. (D) Clinical effect evaluation of mNGS on treatment in immunocompromised (inner circle) and immunocompetent patients (outer circle).