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BALF-mNGS-Derived Microbial Detection Profiles and Their Associations with Clinical Severity in Immunocompromised Patients with Community-Acquired Pneumonia

Year: 2026

Type: article

Abstract: Background: Immunocompromised patients with community-acquired pneumonia (CAP) have heterogeneous pulmonary microbial profiles and frequently experience a severe clinical course. Whether bronchoalveolar lavage fluid metagenomic next-generation sequencing (BALF-mNGS)-derived microbial features are associated with clinical severity in this population remains unclear. Objective: To characterize pulmonary microbial features in immunocompromised patients with CAP and evaluate their association with ICU admission and length of hospital stay (LOHS). Methods: This multicenter retrospective study included 1072 patients with CAP who underwent BALF-mNGS at five hospitals (August 2021–June 2025), including 362 immunocompromised and 710 immunocompetent patients. Microbial diversity, composition, and differentially enriched taxa were compared by immune status. Among immunocompromised patients, taxon–outcome associations were assessed using adjusted logistic and negative binomial regression, with sensitivity analyses additionally adjusting for antibiotic and antifungal exposure before BALF. Results: Immunocompromised patients had higher alpha diversity ( P < 0.001), with limited overall community separation. Five taxa were enriched: Burkholderia multivorans, Klebsiella pneumoniae, Candida glabrata, Candida tropicalis , and Streptococcus pseudopneumoniae . In primary analyses, B. multivorans abundance was associated with ICU admission (adjusted odds ratio [aOR] 1.400, 95% CI 1.088– 1.801; false discovery rate [FDR]-adjusted P =0.045) and longer LOHS (adjusted incidence rate ratio [aIRR] 1.108, 95% CI 1.036– 1.186; FDR-adjusted P =0.014). C. glabrata was associated with longer LOHS (aIRR 1.101, 95% CI 1.023– 1.185; FDR-adjusted P =0.026). K. pneumoniae showed a nominal ICU association that did not survive FDR correction (FDR-adjusted P =0.084). After additional adjustment for antibiotic and antifungal exposure, the associations of B. multivorans and C. glabrata with longer LOHS remained significant (both FDR-adjusted P =0.044), whereas the association between B. multivorans and ICU admission did not (FDR-adjusted P =0.168). Conclusion: BALF-mNGS-derived microbial features showed limited overall community differences but distinct taxon-specific associations with clinical severity. These exploratory findings require further validation before their prognostic or clinical utility can be established. Keywords: immunocompromised patients, community-acquired pneumonia, BALF-mNGS, pulmonary microbiome, clinical severity

Source: Infection and Drug Resistance

DOI: 10.2147/idr.s657668