背景:最近发现替加环素可引起凝血功能紊乱,尤其是低纤维蛋白原血症,这可能会干扰抗菌治疗的给药。本研究旨在探讨替加环素相关低纤维蛋白原血症的发生率、临床特点及危险因素。方法:在这项多中心回顾性研究中,纳入2020年1月至2020年12月在中国9家三级医院接受替加环素或亚胺培南-西司他丁治疗革兰氏阴性菌感染的患者.使用队列和病例对照研究比较基线数据和凝血变量。结果:本研究共纳入了485例接受替加环素治疗的患者和490例接受亚胺培南-西司他丁治疗的患者。与亚胺培南-西司他丁相比,替加环素与纤维蛋白原降低、活化部分凝血活酶时间和凝血酶原时间延长有关(均p<0.001),纤维蛋白原变化最显著(下降48.0%)。替加环素治疗患者的低纤维蛋白原血症发生率>50%,是否具有倾向得分匹配的分析。在基线平衡时,替加环素与亚胺培南-西司他丁的低纤维蛋白原血症的相对风险为2.947(95%CI:2.151-4.039)。替加环素相关的低纤维蛋白原血症导致出血事件发生率较高(12.1%)。然而,停药后的补充治疗对纤维蛋白原水平正常化无影响.替加环素相关的低纤维蛋白原血症的危险因素是治疗持续时间≥6天(比值比[OR]5.214,95%置信区间[CI]2.957-9.191,p<0.001),基线纤维蛋白原<4g/L(OR4.625,95%CI2.911-7.346,p<0.001),累积剂量≥1,000mg(OR2.637,95%CI1.439-4.832,p=0.002),接受CRRT(OR2.436,95%CI1.179-5.031,p=0.016),基线PT>14s(OR2.110,95%CI1.317-3.380,p=0.002)和基线总胆红素>21μmol/L(OR1.867,95%CI1.107-3.147,p=0.019),保护因素为皮肤和软组织感染(OR0.110,95%CI0.026-0.473,p=0.003)。结论:本研究明确替加环素相关低纤维蛋白原血症的临床特点及危险因素,可为临床治疗提供参考。
Background: Tigecycline was recently found to cause coagulation disorders, especially hypofibrinogenemia, which may interfere with the administration of antimicrobial therapy. This
study aimed to investigate the incidence and clinical characteristics of and risk factors for tigecycline-associated
hypofibrinogenemia. Methods: In this multicenter retrospective
study, patients receiving tigecycline or imipenem-cilastatin to treat Gram-negative bacterial infections in nine Chinese tertiary hospitals between January 2020 and December 2020 were enrolled. Baseline data and coagulation variables were compared using cohort and case-control studies. Results: Totals of 485 patients treated with tigecycline and 490 patients treated with imipenem-cilastatin were included in this
study. Compared with imipenem-cilastatin, tigecycline was associated with reduced fibrinogen and prolonged activated partial thromboplastin time and prothrombin time (all p < 0.001), with the most remarkable change in fibrinogen (down by 48.0%). The incidence of hypofibrinogenemia in patients treated with tigecycline was >50%, with propensity score-matched analysis or not. The relative risk of hypofibrinogenemia with tigecycline versus imipenem-cilastatin was 2.947 (95% CI: 2.151-4.039) at baseline balance. Tigecycline-associated hypofibrinogenemia led to a higher incidence (12.1%) of bleeding events. However, none of supplemental therapies after withdrawal had an effect on the normalization of fibrinogen levels. The risk factors for tigecycline-associated hypofibrinogenemia were treatment duration ≥6 days (odds ratio [OR] 5.214, 95% confidence interval [CI] 2.957-9.191, p < 0.001), baseline fibrinogen <4 g/L (OR 4.625, 95% CI 2.911-7.346, p < 0.001), cumulative dose ≥1,000 mg (OR 2.637, 95% CI 1.439-4.832, p = 0.002), receiving CRRT (OR 2.436, 95% CI 1.179-5.031, p = 0.016), baseline PT > 14 s (OR 2.110, 95% CI 1.317-3.380, p = 0.002) and baseline total bilirubin >21 μmol/L (OR 1.867, 95% CI 1.107-3.147, p = 0.019), while the protective factor was skin and soft tissue infection (OR 0.110, 95% CI 0.026-0.473, p = 0.003). Conclusion: The clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia identified in this
study can offer practical reference for the clinical management of patients.