Integrating Plasma mNGS into ICU Antimicrobial Stewardship: A Four-Phase Framework

Background: Plasma metagenomic next-generation sequencing (mNGS) may complement conventional microbiology in critically ill patients, yet its contribution to antimicrobial stewardship in the intensive care unit (ICU) remains unclear. Methods: In this retrospective, single-center observational study, we analyzed 243 paired mNGS-blood culture episodes from 180 ICU patients. We applied a four-phase stewardship framework that integrated clinical severity, biomarker kinetics, blood culture results, mNGS findings, and clinical assessment. Treatment adaptations were classified as escalation, de-escalation, discontinuation, or no change. Multivariable regression identified factors associated with stewardship modification and mortality. Results: Active treatment adaptation occurred in 121 of 243 episodes (49.8%), comprising 61 escalations, 39 de-escalations, and 21 discontinuations. mNGS positivity was independently associated with treatment modification (OR 2.66, 95% CI 1.23-5.75; p = 0.014), whereas blood culture positivity showed an inverse association (OR 0.45, 95% CI 0.20-1.04; p = 0.062). Mortality was primarily linked to physiologic severity and host-response markers, particularly SAPS II and procalcitonin. In-hospital survival did not differ between patients who received stewardship-guided adaptation and those in whom empirical antibiotic therapy was maintained (HR 1.02, 95% CI 0.57-1.81; log-rank p = 0.951). Conclusions: Microbiological findings, particularly mNGS, were associated with antimicrobial treatment adaptation but not independently with mortality. Because mNGS was embedded within a multimodal diagnostic and clinical pathway, its independent contribution cannot be fully separated from concurrent microbiological, biomarker, and clinical information. These findings should be regarded as exploratory and require prospective multicenter validation.