Comparison of bleeding risk and hypofibrinogenemia-associated risk factors between tigecycline with cefoperazone/sulbactam therapy and other tigecycline-based combination therapies.

ABSTRACT

Background: Tigecycline and cefoperazone/sulbactam can cause coagulation disorders; tigecycline may also lead to hypofibrinogenemia, raising safety concerns. This study aimed to investigate whether tigecycline plus cefoperazone/sulbactam increases the risk of bleeding compared with other tigecycline-based combination therapies and identify risk factors for tigecycline-associated hypofibrinogenemia. Methods: In this multi-method, multicenter, retrospective study, coagulation and other baseline variables were compared using a cohort study, and risk factors for hypofibrinogenemia using a case-control study. Results: The 451 enrolled participants were divided into three group tigecycline plus cefoperazone/sulbactam (Group A, 193 patients), tigecycline plus carbapenems (Group B, 200 patients) and tigecycline plus ß-lactams without N-methylthio-tetrazole (NMTT) side chains (Group C, 58 patients). Activated partial thromboplastin time and prothrombin time were prolonged, and fibrinogen declined for all patients after tigecycline-based medication (all p < 0.05). Prothrombin time in Group B was significantly longer than in other groups (p < 0.05), but there were no significant differences in bleeding events between the three groups (p = 0.845). Age greater than 80 years (OR 2.85, 95% CI 1.07-7.60), treatment duration (OR 1.29, 95% CI 1.19-1.41), daily dose (OR 2.6, 95% CI 1.29-5.25), total bilirubin (OR 1.01, 95% CI 1.01-1.02) and basal fibrinogen (OR 1.32, 95% CI 1.14-1.63) were independent risk factors of hypofibrinogenemia. The optimal cut-off for treatment course was 6 days for high-dose and 11 days for low-dose. Conclusion: Tigecycline plus cefoperazone/sulbactam did not increase the risk of bleeding compared with tigecycline plus carbapenem, or tigecycline plus ß-lactam antibiotics without NMTT-side-chains. Coagulation function should be closely monitored in patients receiving tigecycline treatment.