# The impact of the timing of mNGS-guided antibiotic adjustment on clinical outcomes in ICU patients with severe community-acquired pneumonia: a retrospective study

## TL;DR

Adjusting antibiotics early based on mNGS results improves survival in ICU patients with severe pneumonia, especially those with weakened immune systems.

## Contribution

Demonstrates that early mNGS-guided antibiotic adjustment reduces mortality in ICU patients with severe community-acquired pneumonia.

## Key findings

- mNGS detected pathogens more effectively than conventional tests, especially in mixed infections.
- Early antibiotic adjustment based on mNGS results was linked to lower 28-day mortality.
- The benefit of early adjustment was stronger in immunocompromised patients.

## Abstract

Severe community-acquired pneumonia (SCAP) remains a major cause of intensive care unit (ICU) admission and mortality. Prompt pathogen identification and timely administration of appropriate antimicrobial therapy are essential for improving patient outcomes. Although metagenomic next-generation sequencing (mNGS) enables rapid pathogen detection, the prognostic impact of the timing of mNGS-guided antibiotic adjustment remains unclear.

We conducted a multicenter retrospective study of ICU patients diagnosed with SCAP who underwent both bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs). Patients were categorized into early (≤ 72 h) and late (> 72 h) antibiotic adjustment groups based on the interval from ICU admission to the time of antibiotic adjustment guided by mNGS results. Subgroup analyses were performed according to immune status.

In our study, mNGS significantly outperformed conventional microbiological tests (CMTs) in pathogen detection (92.70% vs. 57.18%, P < 0.001), with a particularly higher yield for mixed infections (51.63% vs. 19.14%, P < 0.001). Early mNGS-guided antibiotic adjustment was associated with a significantly reduced 28-day mortality compared to late adjustment (41.98% vs. 53.76%, P = 0.037). Furthermore, multivariate logistic regression analysis confirmed early adjustment as an independent protective factor for 28-day mortality (adjusted OR = 0.44, 95% CI: 0.23–0.83, P = 0.011). In the immunocompromised subgroup, early mNGS-guided adjustment was associated with significantly lower 28-day mortality than late adjustment (39.29% vs. 60.00%, P = 0.029), with a significant interaction observed between timing and immune status (P = 0.042).

Early mNGS-guided antibiotic adjustment is associated with improved survival among ICU patients with SCAP. This benefit is more pronounced in immunocompromised patients, underscoring the importance of early mNGS application to guide antimicrobial decision-making in this vulnerable population.