Clinical characteristics and risk factors of tigecycline-associated hypofibrinogenaemia in critically ill patients

PURPOSE: To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. METHODS: A retrospective case–control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (< 2.0 g/L) and normal fibrinogen (normal) group (≥ 2.0 g/L) to assess the clinical features of patients with tigecycline-associated hypofibrinogenaemia. The traits of patients treated with cefoperazone/sulbactam in the hypofibrinogenaemia group were also analyzed. RESULTS: In total, 127 patients were enrolled in the study, including 71 patients with hypofibrinogenaemia and 56 patients with normal fibrinogen levels. Hypofibrinogenaemia developed at a median of 6 (4–8) days after tigecycline treatment, and the fibrinogen level returned to normal at a median of 3 (3–5) days after tigecycline discontinuation. In the multivariate analysis, intra-abdominal infection (p = 0.005), fibrinogen level at tigecycline initiation (p < 0.001), maintenance dose (p = 0.039), and treatment duration (p = 0.002) were found to be related to hypofibrinogenaemia. Treatment with cefoperazone/sulbactam was not associated with hypofibrinogenaemia (p = 0.681), but patients treated with cefoperazone/sulbactam had a higher incidence of coagulopathy (p = 0.009) and needed more blood products (p = 0.003) than those treated without cefoperazone/sulbactam. CONCLUSION: Tigecycline-associated hypofibrinogenaemia often developed on the 6th (4th–8th) day of tigecycline use and was associated with intra-abdominal infection, fibrinogen level at tigecycline initiation, maintenance dose, and treatment duration of tigecycline but not cefoperazone/sulbactam.