A novel risk stratification model based on creatine kinase and direct bilirubin for identifying severe Chlamydia psittaci pneumonia: a double-center, hypothesis-generating retrospective cohort study

Chlamydia psittaci is a global zoonotic pathogen causing psittacosis, which can progress to severe pneumonia and multi-organ dysfunction. Identifying reliable predictors for severe disease is crucial for improving outcomes, yet current community-acquired pneumonia severity scores may not adequately capture psittacosis-specific systemic manifestations. However, the proposed model is intended to identify patients who already meet criteria for severe pneumonia at presentation, not to predict progression from non-severe to severe disease. We conducted a retrospective cohort study of 36 hospitalized patients with confirmed C. psittaci pneumonia, classified into severe ( n = 11) and non-severe ( n = 25) groups. We employed Firth’s penalized-likelihood logistic regression with bootstrap validation to address small sample size limitations and potential model overfitting. Our analysis establishes a comprehensive framework organized around four key pillars: (1) Radiological evolution - serial computed tomography demonstrated characteristic temporal progression with peak severity at 2 weeks (median Total CT Severity Score: 7), followed by gradual resolution; (2) Biomarker validation - severe cases showed numerically higher creatine kinase (CK) (415.0 vs. 170.0 U/L) and direct bilirubin (DBil) (9.4 vs. 3.8 µmol/L), with exceptional bootstrap stability (relative bias: -8.9% and -7.5%, respectively); however, no variable reached statistical significance ( P < 0.05) in univariable Firth regression, and confidence intervals were wide and included the null; (3) Clinical translation - we developed a risk stratification model categorizing patients into four distinct risk groups based on CK and DBil thresholds; (4) Pathophysiological basis - we propose the “lung-liver-muscle” axis as a hypothesis-generating conceptual framework for systemic disease progression. This exploratory study identifies CK and DBil as stable, readily available biomarkers associated with psittacosis severity at presentation. The integrated four-pillar approach provides hypothesis-generating risk stratification tools and pathophysiological insights, potentially aiding early identification of high-risk patients. All findings require external validation in larger prospective cohorts before any clinical application. Not applicable.