Hypoalbuminemia and reduced sputum microbiome diversity associated with antibiotic treatment failure in nursing and healthcare-associated pneumonia

Abstract

Nursing and healthcare-associated pneumonia (NHCAP) pose significant challenges in older populations, yet factors predicting antibiotic treatment failure remain elusive. This exploratory secondary analysis of a multicenter phase IV trial aimed to identify the clinical and microbiome predictors of treatment failure in patients with NHCAP treated with lascufloxacin. Among the 56 evaluable patients (median age 86 years; cured n = 44, not cured n = 12), paired sputum and tongue samples were analyzed using 16S ribosomal RNA gene clone library sequencing. Alpha diversity was assessed using the Shannon index, Simpson index, observed richness, and Pielou's evenness, whereas beta diversity was calculated using Bray-Curtis dissimilarity and visualized by principal coordinate analysis. Serum albumin was significantly lower in not cured patients (3.0 vs. 3.5 g/dL, p = 0.0497) and emerged as the strongest predictor of treatment failure in univariate logistic regression (odds ratio 0.18, 95% confidence interval 0.05–0.73, p = 0.016). Sputum Pielou's evenness showed a comparable predictive ability (odds ratio 0.010, p = 0.047). The overall microbiome community composition did not differ according to the outcome. Notably, patients with hypoalbuminemia (< 2.85 g/dL) exhibited significantly reduced sputum alpha diversity (Shannon p = 0.034, Simpson p = 0.025, Pielou's evenness p = 0.010). A simple risk stratification combining hypoalbuminemia and denture use identified a high-risk subgroup with markedly elevated treatment failure rates (75.0% vs. 12.5%, p = 0.001). These findings suggest an interconnected pathophysiology linking nutritional status and respiratory microbiome stability in patients with NHCAP. Nutritional status and oral health may be modifiable targets for improving treatment outcomes in high-risk patients.