Risk factors for tigecycline-associated drug-induced liver injury in critically Ill patients: a 2020–2023 retrospective study from a Chinese hospital

Tigecycline is extensively used in Chinese intensive care unit (ICU) for multidrug-resistant infections, yet the profile of its associated drug-induced liver injury (DILI) requires further investigation. Therefore, this study was designed to explore the incidence, identify independent predictors, and characterize the dose-response relationship and timing of tigecycline-associated DILI in critically ill patients. This single-center, retrospective cohort study enrolled all critically ill patients ( n = 309) who received intravenous tigecycline between 2020 and 2023. DILI was diagnosed according to established international biochemical criteria ( n = 71). We employed Pearson correlation analysis and multivariable logistic regression to assess relationships between clinical factors and DILI development. The dose-response relationship between tigecycline exposure and DILI risk was characterized using ROC analysis and generalized additive models (GAM). Time-to-onset of DILI was evaluated using Kaplan-Meier analysis to estimate cumulative incidence and median event time. The incidence of tigecycline-associated DILI was 23.0%. Multivariable analysis identified total duration of tigecycline therapy (OR = 2.01 per week, 95% CI: 1.42–2.92) and cumulative tigecycline dose (OR = 1.51 per gram, 95% CI: 1.19–1.94) as significant independent risk factors. The dose-response relationship was found to be non-linear, with a GAM revealing an initial increase in risk that attenuated at higher cumulative doses ( P < 0.05). The cumulative dose of tigecycline was associated with DILI (AUC = 0.647). The median time to DILI onset among affected patients was 4 days; the Kaplan‑Meier estimate of median DILI‑free survival in the full cohort was 18 days. In patients who develop DILI, the median onset time of 4 days underscores the importance of early hepatic monitoring; the 18‑day Kaplan‑Meier estimate further supports extended vigilance throughout prolonged therapy. Cumulative dose and treatment duration should be managed to mitigate the risk of hepatotoxicity. Not applicable.