Risk Factors for Tigecycline-Associated Drug-Induced Liver Injury in Critically Ill Patients: A 2020-2023 Retrospective Study from a Chinese Hospital

Background 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. Methods 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, generalized additive models (GAM) and generalized linear models (GLM). Time-to-onset of DILI was evaluated using Kaplan-Meier analysis to estimate cumulative incidence and median event time. Results The incidence of tigecycline-associated DILI was 23.0%. Multivariable analysis identified total duration of tigecycline therapy (OR = 2.27 per week, 95% CI: 1.50–3.59) and cumulative tigecycline dose (OR = 1.58 per gram, 95% CI: 1.18–2.14) 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). Kaplan-Meier analysis estimated the median time to DILI onset at 18 days. Conclusions Our findings call for vigilant liver monitoring in patients on tigecycline, particularly beyond 18 days of therapy. Treatment duration and cumulative dose should be actively managed to mitigate the significant risk of drug-induced liver injury.