Real-world pathogen diagnosis in critically ill infected children: A retrospective study using metagenomic next-generation sequencing with different enrichment strategies.

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.