Tigecycline trough concentration and its relationship with hypofibrinogenemia: from onset and duration to recovery

Tigecycline is widely used in intensive care units for the treatment of severe infections caused by multidrug-resistant pathogens. However, the association between tigecycline trough concentration and hypofibrinogenemia (HF) remains insufficiently characterized. This study aimed to explore the association between tigecycline trough concentration and tigecycline-induced hypofibrinogenemia, and analyze the relationships among trough concentration, time to HF onset, HF duration, and fibrinogen recovery time after discontinuation. We conducted a retrospective cohort study of patients with tigecycline plasma concentration measurements from January 2018 to May 2026. Tigecycline-induced HF was defined as fibrinogen < 2.0 g/L and was adjudicated by WHO-UMC criteria. Patients were divided into an HF group and a normal group based on fibrinogen levels. Multivariable logistic regression identified independent risk factors, and receiver operating characteristic analysis determined their cutoff values. Kaplan-Meier curves compared HF cumulative incidence. Correlation analysis was used to analyze the relationships among the trough concentration of tigecycline, the occurrence, duration, and elimination time of HF. Cox regression assessed 30-day mortality. Among 148 enrolled patients, 85 (57.43%) developed tigecycline-induced HF. Multivariable logistic regression identified baseline fibrinogen ( P = 0.022), treatment duration ( P = 0.007), and trough concentration ( P = 0.026) as independent risk factors. The cut-off values were trough concentration ≥ 0.27 µg/mL, duration ≥ 6.50 days, and baseline fibrinogen < 4.55 g/L. HF incidence increased progressively across trough concentration quartiles from 36.11% (Q1) to 82.05% (Q4) (P for trend < 0.001). The median time to HF onset was 7 days, median HF duration was 6 days, and median recovery time after tigecycline discontinuation was 2.5 days. Fibrinogen recovery time after tigecycline discontinuation was positively correlated with HF onset time and HF duration (both P = 0.004). No significant association was observed between HF and 30-day mortality ( P = 0.289). Higher tigecycline trough concentrations were significantly associated with an increased risk of hypofibrinogenemia, with a prominent stepwise risk gradient across quartiles. Recovery time from HF was positively correlated with both HF onset and duration time.