The Clinical Impact of Metagenomic Next-Generation Sequencing (mNGS) Test in Hospitalized Patients with Suspected Sepsis: A Multicenter Prospective Study.

Abstract Background:Next Generation Sequencing (NGS) is a newly developed technology and able to detect pathogens rapidly, which may have great importance in early diagnosis and clinical management of infectious diseases. Our study aimed to assess the diagnostic performance and clinical impact of metagenomic NGS (mNGS) in hospitalized patients with suspected sepsis and analyze the suitable population for mNGS test besides culture.Methods:A multi-center, prospective cohort study was performed. We enrolled eligible patients with hospitalized infection, collected demographic and clinical characteristics, and record the 30-day survival. Blood samples were collected on the day of enrollment to perform blood culture and mNGS test. Diagnostic efficacy of mNGS test and blood culture were calculated, and clinical impact of antibiotic regimen modification based on pathogenic test were also analyzed with SPSS22.0 (SPSS Inc, Chicago, IL).Results:We collected demographic and clinical characteristics of patients, and record the 30-day survival. Blood samples were collected on the day of enrollment to perform blood culture and mNGS test. Diagnostic efficacy of mNGS test and blood culture were calculated, and clinical impact of antibiotic regimen modification based on pathogenic test were also analyzed. A total of 277 patients were enrolled and 162 were diagnosed with sepsis. Among patients with 30-day follow-up data, the mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time [27.0(26.0, 29.0) vs 96.0(72.0, 140.3) hours, P < 0.001] and higher sensitivity (90.54% vs 36.00%, P < 0.001) than blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotics use, and early stage of infection than blood culture. Higher reads of pathogens detected by mNGS was related to 30-day mortality (P=0.002). The mNGS test was capable of guiding antibiotic regimen modification and ameliorating prognosis. Negative mNGS results helped with antibiotic de-escalation safely.Conclusions mNGS technology may be helpful for patients with possible blood-stream infections, especially in fungal infection and for patients with mild symptoms, prior antibiotics use and early stage of infection. Its role in antibiotic stewardship and ameliorating prognosis warrants further study.Trial registrationThe study was registered on the Chinese Clinical Trial Registry (Number: ChiCTR1800019187) on 01/24/2019 (Retrospectively registered).