Serum concentration threshold and risk factors of tigecycline-induced hypofibrinogenaemia in critically ill patients.

Objectives: Hypofibrinogenaemia is a serious adverse reaction associated with tigecycline (TGC) therapy and may lead to the discontinuation of the treatment. This study aimed to explore the relevant factors of TGC-induced hypofibrinogenaemia and determine the thresholds of serum concentration as a predictive indicator of TGC-induced hypofibrinogenaemia.

Methods: A retrospective single-centre study was conducted on patients with severe infection who were treated with TGC. Clinical data and serum concentration parameters were extracted from the electronic medical records of these patients. Patients were divided into the hypofibrinogenaemia group (< 2.0 g/L) and the normal fibrinogen group (≥ 2.0 g/L) in order to evaluate risk factors associated with TGC-induced hypofibrinogenaemia. Logistic regression analysis and receiver operating characteristic curves were utilized to identify the risk factors associated with TGC-induced hypofibrinogenaemia and to establish plasma concentration thresholds as predictive indicators.

Results: A total of 114 patients were enrolled in this study, with 59.6% experiencing hypofibrinogenaemia. The multivariate regression analysis indicated that baseline fibrinogen level, trough concentration (Cmin), peak concentration (Cmax), the concentration at 6 h after the dosing (C6h) and the area under the concentration-time curve over a 24-h period (AUC0-24) were significantly associated with hypofibrinogenaemia (P < 0.05). Furthermore, it was found that AUC0-24 is the optimal predictor of TGC-induced hypofibrinogenaemia. The optimal cut-off for the AUC0-24 of TGC in ICU patients was determined to be 17.03 mg h/L.

Conclusions: TGC exposure is highly predictive of TGC-induced hypofibrinogenaemia. We recommend closely monitoring plasma concentrations of TGC in patients to ensure patient efficacy and safety.