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Metagenomic quantification of Klebsiella pneumoniae burden reveals lung microbiome alterations and poor prognosis in severe community-acquired pneumonia: a multicenter retrospective study

Year: 2026

Type: article

Abstract: Severe community-acquired pneumonia (sCAP) is associated with high mortality and complex microbial etiologies. While metagenomic next-generation sequencing (mNGS) enables comprehensive pathogen detection, the relationship between pathogen burden, lung microbiome alterations, and clinical outcomes remains poorly understood. To investigate the association between Klebsiella pneumoniae burden quantified by mNGS, lung microbiome alterations, and prognosis in patients with sCAP. In this multicenter retrospective study, bronchoalveolar lavage fluid (BALF) samples from intensive care unit patients with sCAP between August 2021 and July 2025 were analyzed. Patients were initially screened based on the detection of K. pneumoniae by mNGS, and infection was subsequently confirmed by microbiological culture. Patients were then stratified into low (1–100), medium (101–10000), and high (> 10000) burden groups according to reads per ten million (RPTM). A total of 162 patients were finally included in this study. Alpha diversity analysis showed significant differences among burden groups, with the highest microbial diversity observed in the medium-burden group and the lowest in the high-burden group ( P < 0.05). Beta diversity analysis demonstrated distinct microbial community structures across groups (PERMANOVA R² = 0.156, P = 0.001). Relative abundance analysis revealed that the high-burden group was dominated by K. pneumoniae , whereas the low and medium-burden groups exhibited more diverse bacterial communities. Increasing K. pneumoniae burden was associated with greater disease severity and worse clinical outcomes, including higher APACHE-II scores, longer mechanical ventilation duration, and prolonged hospital stay (all P < 0.05). The 28-day mortality rate increased significantly across burden groups (17.6%, 34.4%, and 57.6%, P < 0.001). The quantitative burden of K. pneumoniae showed good prognostic performance for 28-day mortality [0.808 (0.739–0.877), sensitivity: 71.20%, specificity: 70.90%] and remained an independent risk factor in multivariable analysis [2.209 (1.604–3.043), P < 0.001]. High K. pneumoniae burden is associated with lung microbiome dysbiosis and poor prognosis in patients with sCAP. Quantitative pathogen burden measured by mNGS may provide a useful biomarker for risk stratification in critically ill patients.

Source: BMC Microbiology

DOI: 10.1186/s12866-026-05897-6