Progression of Fibrinogen Decrease during High Dose Tigecycline Therapy in Critically Ill Patients: A Retrospective Analysis

Treml, Benedikt; Bukumirić, Zoran; Hell, Tobias; Fries, Dietmar; Bachler, Mirjam

doi:10.3390/jcm10204702

Cited by 13 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two previous studies based on in vitro and clinical evidence, respectively, excluded the possibility that tigecycline’s effect on fibrinogen was related to its consumption ( Leng et al, 2019 ; Brandtner et al, 2020 ). Fibrinogen is synthesized in the liver and Treml et al (2021) attributed decreased fibrinogen levels to impaired liver synthesis. Moreover, a rapid loss of mitochondrial activity in hepatic cells was observed after the addition of tigecycline ( Brandtner et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China

Shen

Gao

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China

Shen

Gao

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Some researchers speculate that coagulopathy was associated with increased consumption or impaired synthesis of fibrinogen. 35 The liver is an important organ in synthesizing coagulation factors. Yet, liver function was hardly associated with coagulopathy as assessed by the logistic regression analysis in our study.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Nomogram for Predicting Tigecycline-Related Coagulopathy: A Retrospective Cohort Study

Zeng

et al. 2023

IDR

View full text Add to dashboard Cite

Background Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy. Methods This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by >10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for >3 s than the ULN or reduced serum level of fibrinogen to <2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed. Results Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732–0.851) and 0.730 (0.629–0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy. Conclusion This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.

show abstract

“…It was proposed that the tigecycline’s inhibition of cytokines contributed to the reduced production of FIB [24, 25]. In addition, as FIB was synthetized in the liver and tigecycline could result in aminotransferase enzyme increase, the impaired hepatic function was also associated with tigecycline-induced hypofibrinogenemia [26]. Another possibility could be the increased consumption of FIB due to disseminated intravascular coagulation, but lack of platelet consumption as well as improvement of infection status during tigecycline treatment did not support this hypothesis [8].…”

Section: Discussionmentioning

confidence: 99%

Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study

Lin,

Tan,

Wang

et al. 2023

Pharmacology

View full text Add to dashboard Cite

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.

show abstract

Progression of Fibrinogen Decrease during High Dose Tigecycline Therapy in Critically Ill Patients: A Retrospective Analysis

Cited by 13 publications

References 48 publications

Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China

Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China

Development and Validation of a Nomogram for Predicting Tigecycline-Related Coagulopathy: A Retrospective Cohort Study

Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study

Contact Info

Product

Resources

About