Risk factors and serum concentration thresholds associated with tigecycline-induced hepatotoxicity in critically ill...

Hepatotoxicity is a serious adverse effect associated with tigecycline therapy and may necessitate discontinuation of treatment. Optimal dosing strategies and predictive indicators are urgently needed to improve safety.

This study aims to identify risk factors associated with tigecycline-induced hepatotoxicity and to determine a serum concentration threshold that can serve as a predictive indicator for this adverse event.

This retrospective and single-centre study included patients with severe infections who received tigecycline therapy. Clinical data and serum concentration parameters were extracted from the electronic medical records of these patients. Patients were classified into hepatotoxicity group and normal group to identify the risk factors associated with tigecycline-induced hepatotoxicity. Logistic regression analysis and receiver operating characteristic curve analysis were used to determine the risk factors related to tigecycline-induced hepatotoxicity and to establish a serum-concentration-threshold prediction of this adverse effect.

A total of 151 patients were enrolled in this study, of whom 35.10% developed hepatotoxicity. Multivariate regression analysis revealed that trough concentration (C_min), peak concentration (C_max), concentration at 6 h post-dose (C_6h), 24-h area under the concentration-time curve (AUC_0-24), and concomitant use of voriconazole or statins were all significantly associated with an increased risk of hepatotoxicity (P < 0.05). Furthermore, C_min and C_6h were identified as the optimal predictors of tigecycline-induced hepatotoxicity in ICU patients, with optimal cut-off values of 0.535 and 0.690 mg/L, respectively.

Tigecycline exposure is significantly associated with tigecycline-induced hepatotoxicity. Therefore, we recommend closely monitoring plasma tigecycline concentrations in patients to ensure both therapeutic efficacy and patient safety.