Tigecycline-associated hypofibrinogenemia in a real-world setting

Background Tigecycline is a broad-spectrum antibiotic used to treat infections that do not respond to first-line treatments. High-doses and extended treatments are common; therefore, adverse events might be more frequent and severe than those observed in clinical trials. Several case-reports have referred hypofibrinogenemia in patients who received tigecycline. Objective To analyse the impact of tigecycline use on coagulation parameters, and identify which variables could be related with this. Setting The study was performed at Hospital Universitari Vall Hebron, in Barcelona, Spain. Method Observational, retrospective study. All patients older than 18, who received tigecycline for > 72 h from January 2016 to March 2018 were included. Clinical and laboratory data from before, during and at the end of tigecycline treatment were retrospectively collected. Differences between means were analyzed using the paired-sample Student's t-test. Binary logistic regression was performed to identify risk factors for hypofibrinogenemia. Main outcome measure Mean difference in fibrinogen plasma concentration and INR, before and at the end of tigecycline treatment. Results 78 patients (mean age 65; SD +/- 15.5 years) were identified. The most common indications for tigecycline treatment were abdominal (66%), respiratory tract (16%) and skin&soft tissue (10%) infections. High-dose tigecycline was used in 62% of cases and the median duration of treatment was 12 days. Hypofibrinogenemia occurred in 12 patients, 5 bleeding events were observed and 4 of them required fibrinogen administration. Tigecycline caused significant alterations in fibrinogen plasma concentration (mean decrease 1.76 g/L; IC 95% 1.36 to 2.15) as well as INR (mean increase 0.11; IC 95% 0.05 to 0.17). Both were recovered after treatment cessation. We identified duration of treatment > 4 weeks (OR = 6.6), high-dose tigecycline (OR = 4.75) and high protein C levels (OR = 4.2) as independent variables associated with fibrinogen decrease, but not renal impairment. Conclusions Tigecycline administration has been related with hypofibrinogenemia, especially when high-doses of tigecycline are used. Health professionals should be aware of the potentially severe tigecycline-associated hypofibrinogenemia and monitor coagulation during treatment, especially when high-doses of tigecycline are used.