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Published on: August 25, 2018
Real-world pathogen diagnosis in critically ill infected children: A retrospective study using metagenomic
Huili Shen1, Xiaolei Zhang1, Junfeng Xu2
1Department of Critical Care Medicine, and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Background:
Study on the clinical pathogen diagnosis in large cohort of critically ill children using metagenomic next-generation sequencing (mNGS) with different enrichment strategies has been limited.
Methods:
763 samples were enrolled and we summarized the clinical pathogen diagnosis and compared the performance between mNGS and clinical microbial tests (CMTs) in different sample types, as well as between shotgun-based (S-mNGS) and hybrid capture-based mNGS (C-mNGS).
Results:
A total of 93 clinical diagnosed pathogens were identified from763 samples with suspected infections, with a positive rate of 60.16 %. Respiratory specimens had the highest positive rate (90.73 %, 235/259), while the lowest was cerebrospinal fluid (26.94 %, 59/219). mNGS showed higher sensitivity (90.85 % vs. 83.66 %, P = 0.001), specificity (77.30 % vs. 67.43 %, P = 0.007), positive predictive value (PPV, 85.80 % vs. 79.50 %, P = 0.01), negative predictive value (NPV, 84.84 % vs. 73.21 %, P < 0.001), and accuracy (85.45 % vs. 77.20 %, P < 0.001) than CMTs. The corrected true positive rate of mNGS was higher than CMTs (83.88 % vs. 75.60 %, P = 0.002), and its advantage in virus detection was more obvious (OR=1.39, 95 %CI: 1.08-1.78, P = 0.010). S-mNGS and C-mNGS shown significantly higher sensitivity and accuracy than CMTs. However, the total true positive rate between S-mNGS and C-mNGS were close (83.15 % vs. 85.00 %, P = 0.600). According to the mNGS results, the adjusted pathogen diagnosis rate was 45.48 % (417/763), and the adjusted anti-infection strategy ratio was 42.86 % (327/763).
Conclusions:
mNGS provided an efficient pathogen diagnosis method for critically ill children with suspected infection. Different enrichment strategies of mNGS can play their respective advantages in clinical practice.
Insights
Metagenomic next-generation sequencing (mNGS) offers efficient pathogen diagnosis in critically ill children, outperforming traditional clinical microbial tests (CMTs). Different mNGS enrichment strategies provide distinct clinical advantages.
Area of Science:
- Clinical microbiology
- Genomics
- Infectious disease diagnostics
Background:
- Limited studies exist on clinical pathogen diagnosis in critically ill children using metagenomic next-generation sequencing (mNGS).
- Evaluating different mNGS enrichment strategies in this population is crucial.
Purpose of the Study:
- To assess the performance of mNGS compared to clinical microbial tests (CMTs) for pathogen diagnosis in critically ill children.
- To compare shotgun-based mNGS (S-mNGS) and hybrid capture-based mNGS (C-mNGS) performance.
Main Methods:
- Analysis of 763 samples from critically ill children with suspected infections.
- Comparison of mNGS and CMTs across various sample types.
- Evaluation of S-mNGS and C-mNGS methodologies.
Main Results:
- mNGS demonstrated higher sensitivity, specificity, PPV, NPV, and accuracy than CMTs.
- Respiratory specimens showed the highest positive rate; cerebrospinal fluid had the lowest.
- S-mNGS and C-mNGS showed superior performance over CMTs, with comparable true positive rates between S-mNGS and C-mNGS.
Conclusions:
- mNGS is an effective method for diagnosing pathogens in critically ill children.
- Specific mNGS enrichment strategies offer unique benefits for clinical application.
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