Independent Risk Factors for In-Hospital Mortality in Non-HIV Adult Tuberculous Meningitis: A Large Retrospective Cohort Study from China

Abstract Background: Tuberculous meningitis (TBM) represents the most severe form of tuberculosis and is associated with high short-term mortality, particularly in low- and middle-income countries. However, robust evidence identifying predictors of in-hospital mortality among non-HIV adult TBM patients remains limited. Objective: To identify independent clinical and laboratory predictors of in-hospital mortality among adults with TBM. Methods: We conducted a retrospective cohort study including adult patients with suspected TBM admitted to Changsha Central Hospital, Hunan Province, China, between October 1, 2013, and October 1, 2023. TBM cases were classified as definite, probable, or possible using standardized diagnostic criteria. In-hospital mortality was the primary outcome. Candidate predictors were initially screened using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable analysis with Firth-penalized logistic regression to address potential separation bias. Multicollinearity was assessed using variance inflation factors (VIF). Model discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUC), bootstrap calibration, and the Hosmer–Lemeshow goodness-of-fit test. Results: A total of 1,346 adult patients were included (32.2% definite, 62.9% probable, and 4.8% possible TBM). The median age was 47 years (interquartile range [IQR], 30–62), and 68.0% were female. Overall in-hospital mortality was 12.26% (165/1,346). Multivariable analysis identified drug-induced hepatitis, hydrocephalus, renal failure, immunodeficiency, positive cerebrospinal fluid (CSF) tuberculosis antibody, elevated procalcitonin (PCT) levels, and advanced age as independent predictors of increased in-hospital mortality. Higher CSF glucose levels showed a protective trend. The final model included 16 predictors, demonstrated minimal multicollinearity (maximum VIF 4.0; mean VIF 1.28), and showed excellent performance (AUC 0.917; bootstrap mean absolute calibration error 0.014; Hosmer–Lemeshow p = 0.098). Conclusion: Among non-HIV adult patients with TBM, drug-induced hepatitis, hydrocephalus, renal failure, immunodeficiency, positive CSF tuberculosis antibody, elevated PCT levels, and advanced age are key independent predictors of in-hospital mortality. These findings may assist clinicians in identifying patients at higher risk of in-hospital mortality in high-burden settings.