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

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...

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Autores principales: Brandtner, Anna, Bachler, Mirjam, Fries, Dietmar, Hermann, Martin, Ruehlicke, Jacqueline, Fux, Vilmos, Griesmacher, Andrea, Niederwanger, Christian, Hell, Tobias, Treml, Benedikt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168332/
https://www.ncbi.nlm.nih.gov/pubmed/32074981
http://dx.doi.org/10.3390/antibiotics9020084
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author Brandtner, Anna
Bachler, Mirjam
Fries, Dietmar
Hermann, Martin
Ruehlicke, Jacqueline
Fux, Vilmos
Griesmacher, Andrea
Niederwanger, Christian
Hell, Tobias
Treml, Benedikt
author_facet Brandtner, Anna
Bachler, Mirjam
Fries, Dietmar
Hermann, Martin
Ruehlicke, Jacqueline
Fux, Vilmos
Griesmacher, Andrea
Niederwanger, Christian
Hell, Tobias
Treml, Benedikt
author_sort Brandtner, Anna
collection PubMed
description 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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spelling pubmed-71683322020-04-22 Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System Brandtner, Anna Bachler, Mirjam Fries, Dietmar Hermann, Martin Ruehlicke, Jacqueline Fux, Vilmos Griesmacher, Andrea Niederwanger, Christian Hell, Tobias Treml, Benedikt Antibiotics (Basel) Article 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. MDPI 2020-02-14 /pmc/articles/PMC7168332/ /pubmed/32074981 http://dx.doi.org/10.3390/antibiotics9020084 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brandtner, Anna
Bachler, Mirjam
Fries, Dietmar
Hermann, Martin
Ruehlicke, Jacqueline
Fux, Vilmos
Griesmacher, Andrea
Niederwanger, Christian
Hell, Tobias
Treml, Benedikt
Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
title Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
title_full Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
title_fullStr Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
title_full_unstemmed Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
title_short Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
title_sort tigecycline interferes with fibrinogen polymerization independent of peripheral interactions with the coagulation system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168332/
https://www.ncbi.nlm.nih.gov/pubmed/32074981
http://dx.doi.org/10.3390/antibiotics9020084
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