Methicillin-resistant Staphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration
| Autor: | Jeffrey T. Holloway, Robert A. Campbell, Zechariah Franks, Matthew T. Rondina, Andrew S. Weyrich, James E. Marvin, Adriana Vieira de Abreu, Guy A. Zimmerman, Bjoern F. Kraemer |
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| Rok vydání: | 2013 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Time Factors medicine.drug_class 030106 microbiology Antibiotics medicine.disease_cause Drug Administration Schedule Monocytes Article Mice 03 medical and health sciences chemistry.chemical_compound Tissue factor Thrombin Cell-Derived Microparticles Vancomycin Sepsis Acetamides Animals Humans Medicine Blood Coagulation Oxazolidinones Inflammation business.industry Linezolid Interleukin Thrombosis Hematology Staphylococcal Infections biochemical phenomena metabolism and nutrition Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Mice Inbred C57BL 030104 developmental biology chemistry Staphylococcus aureus Immunology Cytokines Inflammation Mediators business medicine.drug |
| Zdroj: | Thrombosis and Haemostasis. 109:684-695 |
| ISSN: | 2567-689X 0340-6245 |
| DOI: | 10.1160/th12-08-0543 |
| Popis: | SummaryMethicillin-resistant Staphylococcus aureus (MRSA) induces a prothrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSA sepsis may improve outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thrombo-inflammatory 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 time- and 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. |
| Databáze: | OpenAIRE |
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