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Marie-Joelle Virolle
Open AccessArticle

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

1
Laboratory for Inflammation Research, Department for Internal Medicine, Division of Intensive Care and Emergency Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria
2
Institute for Sports, Alpine Medicine and Health Tourism, Private University for Health Sciences, Medical Informatics and Technology GmbH, 6060 Hall in Tirol, Austria
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Department of General and Surgical Intensive Care, Medical University Innsbruck, 6020 Innsbruck, Austria
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Central Institute of Medical and Chemical Laboratory Diagnostics, University Hospitals of Innsbruck, Innsbruck 6020, Austria
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Department for Pediatrics, Pediatrics I, Intensive Care Unit, Medical University Innsbruck, 6020 Innsbruck, Austria
6
Department of Mathematics, Faculty of Mathematics, Computer Science and Physics, University Innsbruck, 6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
Antibiotics 2020, 9(2), 84; https://doi.org/10.3390/antibiotics9020084
Received: 20 January 2020 / Revised: 7 February 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
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.
Keywords: tigecycline; fibrinogen; bleeding; real time live confocal analysis; hepatocyte cell culture tigecycline; fibrinogen; bleeding; real time live confocal analysis; hepatocyte cell culture
MDPI and ACS Style

Brandtner, A.; Bachler, M.; Fries, D.; Hermann, M.; Ruehlicke, J.; Fux, V.; Griesmacher, A.; Niederwanger, C.; Hell, T.; Treml, B. Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System. Antibiotics 2020, 9, 84.

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