Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort

Abstract

Background: Plasma metagenomic next-generation sequencing (mNGS) has the potential to detect thousands of different organisms with a single test. There are limited data on the real-world impact of mNGS and even less guidance on the types of patients and clinical scenarios in which mNGS testing is beneficial. Methods: A retrospective review of patients who had mNGS testing as part of routine clinical care at Texas Children's Hospital from June 2018-August 2019 was performed. Medical records were reviewed for pertinent data. An expert panel of infectious disease physicians adjudicated each unique organism identified by mNGS for clinical impact. Results: There were 169 patients with at least one mNGS test. mNGS identified a definitive, probable or possible infection in 49.7% of patients. mNGS led to no clinical impact in 139 patients (82.2%), a positive impact in 21 patients (12.4%), and a negative impact in 9 patients (5.3%). mNGS identified a plausible cause for infection more often in immunocompromised patients than in immunocompetent patients (55.8% vs. 30.0%, P = 0.006). Positive clinical impact was highest in patients with multiple indications for testing (37.5%, P = 0.006) with deep-seated infections, overall, being most often associated with a positive impact. Conclusion: mNGS testing has a limited real-world clinical impact when ordered indiscriminately. Immunocompromised patients with well-defined deep-seated infections are likely to benefit most from testing. Further studies are needed to evaluate the full spectrum of clinical scenarios for which mNGS testing is impactful.

Clinical Application and Influencing Factor Analysis of Metagenomic Next-Generation Sequencing (mNGS) in ICU Patients With Sepsis

“…The earlier studys ( Geng et al., 2021 ; Yan et al., 2021 ) showed that low immunity was associated with multiple infections. Niles et al., ( Niles et al., 2022 ) in a retrospective study of 169 participants, showed that immune-related patients were more likely to obtain multiple microbial results from mNGS than patients with normal immune function.…”

Sequence-based diagnostics and precision medicine in bacterial and viral infections: from bench to bedside

“…Pertinent mcfDNA studies that include immunocompromised patients are summarized in Table 2. Overall, the clinical impact of Karius testing has varied widely across studies (range 7–80%) [7,41 ▪ ,42,43 ▪ ,44–47], which may be partly related to the absence of standardized impact definitions. Factors associated with positive clinical impact included immunocompromised status, infectious diseases/stewardship-led approval and support for interpreting results [49].…”

Metagenomic next-generation sequencing in osteoarticular infections with a focus on pediatrics: current concepts and clinical applications

“…There have also been studies of cfNGS showing limited benefit. Niles et al ( 83 ) performed a retrospective review of 169 pediatric patients who underwent cfNGS and found that cfNGS had a negative clinical impact in 5.3% (9/169), a positive impact in 12.4% (21/169), and no impact in 82.2% (139/169) of patients. The authors concluded that cfNGS had some clinical impact on immunocompromised patients but had limited clinical impact when ordered for all patients.…”

“…They concluded that with much more research, mNGS has the potential to become the next frontier of clinical microbiology and will likely be included in the clinicians' armamentarium for treating infectious diseases. Multiple other studies have addressed clinical impact, but all conclude that more research is needed to determine this definitively ( 5 , 30 , 50 , 82 , 83 , 96 , 97 , 98 ).…”