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METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS-INDUCED THROMBOINFLAMMATORY RESPONSE IS REDUCED WITH TIMELY ANTIBIOTIC ADMINISTRATION
Citocinas
Tromboplastina
Trombina
Staphylococcus aureus Resistente à Meticilina
Author
Affilliation
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA / University of Utah Health Sciences Center. Salt Lake City, Utah, USA.
University of Utah Health Sciences Center. Salt Lake City, Utah, USA / Universitaet München. Medizinische Klinik und Poliklinik I, Klinikum. München, Germany.
University of Utah Health Sciences Center, Salt Lake City, Utah, USA / University of Utah. School of Medicine. Department of Internal Medicine. Pulmonary and Critical Care Medicine. Salt lake City, Utah, USA.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA / University of Utah Health Sciences Center. Salt Lake City, Utah, USA.
3University of Utah Health Sciences Center, Salt Lake City, Utah, USA / University of Utah. School of Medicine . Divisions of General Internal Medicine. Salt Lake City, Utah, USA.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA / University of Utah Health Sciences Center. Salt Lake City, Utah, USA.
University of Utah Health Sciences Center. Salt Lake City, Utah, USA / Universitaet München. Medizinische Klinik und Poliklinik I, Klinikum. München, Germany.
University of Utah Health Sciences Center, Salt Lake City, Utah, USA / University of Utah. School of Medicine. Department of Internal Medicine. Pulmonary and Critical Care Medicine. Salt lake City, Utah, USA.
University of Utah. School of Medicine. Molecular Medicine Program. Salt lake City, Utah, USA / University of Utah Health Sciences Center. Salt Lake City, Utah, USA.
3University of Utah Health Sciences Center, Salt Lake City, Utah, USA / University of Utah. School of Medicine . Divisions of General Internal Medicine. Salt Lake City, Utah, USA.
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) induces a pro-thrombotic and proinflammatory
milieu. Although timely antibiotic administration in MRSA sepsis may improve
outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thromboinflammatory
cellular responses remains unexplored. Using a newly developed human whole
blood model and an in vivo mouse model of MRSA infection, we examined how antibiotics
inhibit MRSA induced thrombo-inflammatory pathways. Human whole blood was inoculated with
MRSA. Thrombin generation and inflammatory cytokine synthesis was measured in the presence
or absence of linezolid and vancomycin. C57BL/6 mice were injected with MRSA and the effect
of vancomycin administration was examined. MRSA accelerated thrombin generation in a timeand
concentration-dependent manner and induced the release of cytokines, including interleukin
(IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1. The increase in thrombin generation and
inflammatory responses was mediated through the synthesis of tissue factor and cytokines,
respectively, and the release of microparticles. The early administration of antibiotics restored
normal thrombin generation patterns and significantly reduced the synthesis of cytokines. In
contrast, when antibiotic administration was delayed, thrombin generation and cytokine synthesis
were not significantly reduced. In mice infected with MRSA, early antibiotic administration
reduced thrombin anti-thrombin complexes and cytokine synthesis, whereas delayed antibiotic administration did not. These data provide novel mechanistic evidence of the importance of
prompt antibiotic administration in infectious syndromes.
DeCS
AntibacterianosCitocinas
Tromboplastina
Trombina
Staphylococcus aureus Resistente à Meticilina
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