Associations of recorded in-hospital linezolid and fluoroquinolone exposure with mortality and documented drug-induced liver injury in non-HIV tuberculous meningitis: a propensity score-weighted real-world cohort study.

Background: Tuberculous meningitis (TBM) remains the most severe form of tuberculosis. Linezolid- and fluoroquinolone-containing regimens are used in clinical practice, but their associations with mortality and specific toxicities in non-HIV TBM remain uncertain. Methods: We conducted a single-center retrospective cohort study of non-HIV patients with TBM hospitalized between October 2013 and January 2024. The exposures were recorded linezolid use, fluoroquinolone-class use, and combined linezolid-fluoroquinolone use during the index hospitalization. Each indexed exposure was compared with no recorded use of that exposure; for the combined analysis, the comparator was not-both exposure (either agent alone or neither agent). Outcomes were in-hospital all-cause death and drug-induced liver injury (DILI) documented during the index hospitalization. Propensity score-based inverse probability of treatment weighting and doubly robust weighted logistic regression with model-robust sandwich standard errors were used. Propensity score matching, complete-case analysis, 20-dataset multiple imputation, a sensitivity analysis restricted to age, sex, diabetes mellitus, and immunodeficiency, and subgroup interaction analyses were performed. Results: Among 1,574 patients, 187 died in hospital and 116 had DILI documented during the index hospitalization. Linezolid was recorded in 996 patients, fluoroquinolone-class therapy in 859, and both in 556. After weighting, all modeled covariates had absolute standardized mean differences below 0.10. None of the three recorded exposures was significantly associated with in-hospital death or DILI documented during the index hospitalization. Complete-case, multiple-imputation, and temporally restricted sensitivity estimates were directionally consistent with the primary results. None of the prespecified exposure-by-subgroup interactions was statistically significant after outcome-specific multiplicity adjustment. Conclusions: Recorded in-hospital linezolid, fluoroquinolone, and combined exposure were not significantly associated with in-hospital death or DILI documented during the index hospitalization in this cohort. The estimates apply to recorded inpatient exposure and DILI and do not establish the effects of treatment initiation at a defined time or the overall safety of these regimens. For DILI, the data do not establish that the liver event occurred after linezolid or fluoroquinolone initiation.