Clinical Pharmacist in Pharmacy Department, Hospital Universitari Vall Hebron, Barcelona, Spain.
Servei de Farmàcia, Vall d'Hebron Hospital Campus, Paseo Valle de Hebrón, 119-129, 08035, Barcelona, Spain.
Int J Clin Pharm. 2020 Aug;42(4):1184-1189. doi: 10.1007/s11096-020-01072-7. Epub 2020 Jun 5.
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.
替加环素是一种广谱抗生素，用于治疗对一线治疗无反应的感染。高剂量和延长治疗是常见的；因此，不良反应可能比临床试验中观察到的更频繁和更严重。一些病例报告提到接受替加环素治疗的患者出现低纤维蛋白原血症。目的：分析替加环素使用对凝血参数的影响，并确定哪些变量可能与之相关。地点：该研究在西班牙巴塞罗那的 Vall Hebron 大学医院进行。方法：观察性、回顾性研究。纳入 2016 年 1 月至 2018 年 3 月期间接受替加环素治疗>72 小时的年龄>18 岁的所有患者。回顾性收集替加环素治疗前、治疗期间和治疗结束时的临床和实验室数据。使用配对样本学生 t 检验分析均值差异。采用二项逻辑回归分析低纤维蛋白原血症的危险因素。主要观察指标：替加环素治疗前后纤维蛋白原血浆浓度和 INR 的平均差异。结果：共确定 78 例患者（平均年龄 65 岁±15.5 岁）。替加环素治疗的最常见适应证为腹部（66%）、呼吸道（16%）和皮肤软组织（10%）感染。62%的病例使用高剂量替加环素，中位治疗时间为 12 天。12 例患者出现低纤维蛋白原血症，观察到 5 例出血事件，其中 4 例需要纤维蛋白原治疗。替加环素显著改变纤维蛋白原血浆浓度（平均降低 1.76g/L；95%CI 1.36 至 2.15）和 INR（平均增加 0.11；95%CI 0.05 至 0.17）。停药后均恢复正常。我们发现治疗时间>4 周（OR=6.6）、高剂量替加环素（OR=4.75）和高蛋白 C 水平（OR=4.2）是与纤维蛋白原降低相关的独立变量，但与肾功能不全无关。结论：替加环素的使用与低纤维蛋白原血症有关，尤其是使用高剂量替加环素时。医务人员应注意潜在的严重替加环素相关低纤维蛋白原血症，并在治疗期间监测凝血情况，尤其是使用高剂量替加环素时。
