Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

Zhang, Qian; Zhou, Suming; Zhou, Jing

doi:10.1128/aac.04305-14

Cited by 59 publications

(60 citation statements)

References 15 publications

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“…One could hypothesize that high-dose treatment with tigecycline is a possible risk factor for hypofibrinogenemia which is supported by the observations of Routsi et al who found high doses of this drug leading to hypofibrinogenemia [4]. Moreover, Zhang et al described a dose dependent decrease of fibrinogen levels [5].…”

Section: Discussionmentioning

confidence: 81%

“…A described side effect during tigecycline therapy is coagulopathy. Three small-scale studies reported effects of tigecycline on coagulation [3][4][5]. A clinical trial observed decreased fibrinogen levels as assessed by the classical Clauss method during high-dose treatment with tigecycline in a group of 45 intensive care patients [4].…”

Section: Introductionmentioning

confidence: 99%

“…and during high dose (2 × 100 mg iv. per day) treatment with clinical bleeding in six patients [5]. Hakeam et al reported decreased fibrinogen levels during tigecycline treatment as compared to imipenem-cilastatin after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with peritoneal carcinomatosis [6].…”

Section: Introductionmentioning

confidence: 99%

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Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System

Brandtner

Bachler²,

Fries

et al. 2020

Antibiotics

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Tigecycline offers broad anti-bacterial coverage for critically ill patients with complicated infections. A described but less researched side effect is coagulopathy. The aim of this study was to test whether tigecycline interferes with fibrinogen polymerization by peripheral interactions. To study the effect of unmetabolized tigecycline, plasma of healthy volunteers were spiked with increasing concentrations of tigecycline. In a second experimental leg, immortalized human liver cells (HepG2) were treated with the same concentrations to test an inhibitory effect of hepatic tigecycline metabolites. Using standard coagulation tests, only the activated thromboplastin time in humane plasma was prolonged with increasing concentrations of tigecycline. Visualization of the fibrin network using confocal live microscopy demonstrated a qualitative difference in tigecycline treated experiments. Thrombelastometry and standard coagulation tests did not indicate an impairment of coagulation. Although the discrepancy between functional and immunologic fibrinogen levels increased in cell culture assays with tigecycline concentration, fibrinogen levels in spiked plasma samples did not show significant differences determined by functional versus immunologic methods. In our in vitro study, we excluded a direct effect of tigecycline in increasing concentrations on blood coagulation in healthy adults. Furthermore, we demonstrated a rapid loss of mitochondrial activity in hepatic cells with supra-therapeutic tigecycline dosages.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System

Brandtner

Bachler²,

Fries

et al. 2020

Antibiotics

View full text Add to dashboard Cite

show abstract

“…The highest tolerated dose was 200 mg per day (Muralidharan et al, 2005). However, a recent study showed that high doses of tigecycline are associated with decreased fibrinogen level along with prolonged prothrombin time, activated partial thromboplastin time, and thrombin time (Zhang et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country: A Compromised Outcome

et al. 2017

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Introduction: With the rise in antibiotic resistance, tigecycline has been used frequently in off-label indications, based on its in-vitro activity against multidrug-resistant organisms. In this study, our aim was to assess its use in approved and unapproved indications.Materials and Methods: This is a retrospective chart review evaluating a 2-year experience of tigecycline use for > 72 h in 153 adult patients inside and outside critical care unit from January 2012 to December 2013 in a Lebanese tertiary-care hospital.Results: Tigecycline was mostly used in off-label indications (81%) and prescribed inside the critical care area, where the number of tigecycline cycles was 16/1,000 patient days. Clinical success was achieved in 43.4% of the patients. In the critically ill group, it was significantly higher in patients with a SOFA score <7 using multivariate analysis (Odds Ratio (OR) = 12.51 [4.29–36.51], P < 0.0001). Microbiological success was achieved in 43.3% of patients. Yet, the univariate and adjusted multivariate models failed to show a significant difference in this outcome between patients inside vs. outside critical care area, those with SOFA score <7 vs. ≥ 7, and in FDA-approved vs. off-label indications. Total mortality reached ~45%. It was significantly higher in critically ill patients with SOFA score ≥7 (OR = 5.17 [2.43–11.01], P < 0.0001) and in off-label indications (OR = 4.00 [1.30–12.31], P = 0.01) using an adjusted multivariate model. Gram-negative bacteria represented the majority of the clinical isolates (81%) and Acinetobacter baumannii predominated (28%). Carbapenem resistance was present in 85% of the recovered Acinetobacter, yet, more than two third of the carbapenem-resistant Acinetobacter species were still susceptible to tigecycline.Conclusion: In our series, tigecycline has been mostly used in off-label indications, specifically in severely ill patients. The outcome of such infections was not inferior to that of FDA-approved indications, especially inside critical care area. The use of this last resort antibiotic in complicated clinical scenarios with baseline microbiological epidemiology predominated by extensively-drug resistant pathogens ought to be organized.

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“…A review of the adverse event profile of TGC suggested that off-label use rarely causes unexpected adverse events, presumably due to usage with extreme caution. Nevertheless, more recently, the use of TGC has been associated with decreased fibrinogen levels, especially at high doses [9]. …”

Section: Introductionmentioning

confidence: 99%

AcinetobacterProsthetic Joint Infection Treated with Debridement and High-Dose Tigecycline

et al. 2016

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Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline.Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30–60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is probably under-dosed for the treatment of implant and biofilm associated infections.

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Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

Cited by 59 publications

References 15 publications

Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System

Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System

Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country: A Compromised Outcome

AcinetobacterProsthetic Joint Infection Treated with Debridement and High-Dose Tigecycline

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