Abstract
BACKGROUND AND OBJECTIVE: Chlamydia psittaci and Legionella pneumophila are common atypical pathogens that cause severe community-acquired pneumonia (CAP). This study aimed to compare the clinical features and outcomes of Chlamydia psittaci pneumonia (CPP) and Legionella pneumophila pneumonia (LPP) identified using next-generation sequencing (NGS) for accurate identification. METHODS: This retrospective study included 68 patients with CPP and 42 patients with LPP. All cases were confirmed by metagenomic or targeted next-generation sequencing (mNGS/tNGS) of bronchoalveolar lavage fluid, serum, or sputum samples. RESULTS: Patients with LPP had a higher prevalence of diabetes and were predominantly male. Poultry contact was common in CPP (64.7% vs. 14.3%), whereas recent travel was associated with LPP (47.6% vs. 2.9%). LPP presented with increased extrapulmonary symptoms. Inflammatory marker levels were higher in LPP, including leukocytosis, neutrophilia, C-reactive protein, and procalcitonin (all p < 0.05). Organ dysfunction was more frequent in LPP, with higher creatinine levels. Patients with LPP had more severe hypoxemia, required more respiratory support, and had higher intensive care admission rates. Targeted therapy guided by NGS was effective, with no significant differences in mortality or hospital stay between the two groups. CONCLUSION: LPP demonstrated greater initial clinical and laboratory severity compared to CPP. Under NGS-guided targeted therapy, both groups achieved comparable outcomes. The observational finding that both pathogens respond to azithromycin and cause severe disease when left undetected underscore the value of guideline-recommended β-lactams/macrolide combination therapy in CAP settings, particularly where these intracellular pathogens remain undiagnosed without NGS.