Clinical application of metagenomic next-generation sequencing (mNGS) in children with suspected bloodstream infection.

Abstract

Background: Accurate and comprehensive pathogen diagnosis methods are urgently required for the diagnosis of bloodstream infection (BSI).This study retrospectively evaluated the clinical application of metagenomic next-generation sequencing (mNGS) in children with suspected BSI.

Methods: Between July 8, 2021 to December 31, 2022, mNGS tests and conventional methods tests (CMTs) were performed simulataneously on samples from children with suspected BSI. The diagnostic performance of mNGS was assessed in comparison CMTs .

Results: A total of 191 patients with suspected BSI were included in the final analysis after excluding 9 patients due to lost to follow-up or duplicated entries. The mNGS yielded positive results in 111 cases, with a positive rate of 58.1% (111/191), significantly higher than that of CMTs (13.1%, 25/191) (P < 0.05). Using CMTs as standard, the sensitivity, specificity, positive predictive value and negative predictive value for mNGS and CMTs were 73.8% vs. 25.0%, 54.2% vs. 96.3%, 55.9% vs. 84.0%, and 72.5% vs. 62.0%, respectively. Among 111 mNGS-positive cases, 46 cases (41.4%) showed ploymicrobial infections, with Torque teno virus, human betaherpesvirus 5, and human gammaherpesvirus 4 being most frequently identified pathogens. Of them, 62 cases (55.9%) were clinically diagnosed as BSI regarded as true positive results, while 49 cases (44.1%) positive for pathogens were diagnosed as non-BSI. The diagnostic time of mNGS was significantly shorter than that of CMTs (30.6 ± 7.7 h vs. 70.5 ± 11.6 h, P < 0.05). It is worth noting that mNGS results guided adjustments to antimicrobial therapy in 50.8% (97/191) patients, including escalation in 74 cases and de-escalation in 23 cases.

Conclusions: The mNGS significantly improves the detection rate for the pathogens in children with suspected BSI, especially for viruses, which serve as a complement to CMTs.