Metagenomic next-generation sequencing (mNGS) guides targeted antibiotic therapy and reduces mortality in sepsis: a propensity-matched retrospective cohort study.

OBJECTIVES: To evaluate the impact of metagenomic next-generation sequencing (mNGS)-guided antimicrobial therapy on mortality in patients with sepsis. METHODS: A retrospective cohort study was conducted on 303 patients with sepsis admitted to the ICU between January 2021 and December 2022. Patients were divided into the mNGS group (93 cases) and the non-mNGS group (130 cases). The primary outcome was 28-day mortality. Statistical analysis included binary logistic regression, propensity score matching (PSM), and mediation analysis. RESULTS: A 1:1 PSM was performed for the original cohort (n = 303), yielding a matched cohort of 160 patients (n = 80 each group). In the matched cohort, antibiotics adjustments based on pathogenic results were more frequent and the 28-day mortality was lower in the mNGS group than in the non-mNGS group (P < 0.01). Binary logistic regression further confirmed significant associations of mNGS detection with a higher likelihood of antibiotic adjustment (odds ratio [OR] = 29.742, 95% CI [10.630, 83.170]) and shorter time to antibiotic adjustment (OR = 0.671, 95% CI [0.566, 0.795]), also with less skin and soft tissue infection (OR = 0.089, 95% CI [0.009, 0.880]) and abdominal infection (OR = 0.206, 95% CI [0.052, 0.812]). Each 1-point increase in the Sequential Organ Failure Assessment (SOFA) score was associated with a 16.9% higher risk of mortality (OR = 1.169, CI [1.054, 1.297]). The decision of antibiotic adjustment (OR = 0.252, CI [0.101, 0.627]) was negatively associated with 28-day mortality. The treatments of mechanical ventilation (OR = 4.260, CI [1.783, 10.181]) and continuous renal replacement therapy (CRRT) (OR = 4.253, CI [2.117, 8.541]) were positively related to the 28-day mortality. The mediation analysis indicated the total effect of mNGS detection on 28-day mortality was significant (Z = − 2.754, P = 0.006), while the indirect effect through antibiotics adjustment was not significant (Z = 0.367, P = 0.714). CONCLUSION: The mNGS detection facilitates antibiotic adjustment and is associated with reduced 28-day mortality in septic ICU patients. These findings highlight its potential for broader clinical application.