Methicillin-resistant Staphylococcus aureus - induced thrombo-inflammatory response is reduced with timely antibiotic administration.

Jan 2013

Franks Z, Campbell RA, Vieira de Abreu A, Holloway JT, Marvin JE, Kraemer BF, Zimmerman GA, Weyrich AS, Rondina MT.

Source

Matthew T. Rondina, MD, University of Utah, Department of Internal Medicine, 50 North Medical Drive, Room 4B120, SLC, Utah 84132, USA, Tel.: +1 801 581 7818, Fax: +1 801 585 1393, E-mail: matthew.rondina@hsc.utah.edu.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA ) induces a pro-thrombotic 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 MRSAand 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.

Schattauer

Superbug Hideout: Finding MRSA in U.S.Wastewater Treatment Plants

Superbug Hideout: Finding MRSA in U.S.Wastewater Treatment Plants

Nov 2012

For many years, the “superbug” methicillin-resistant Staphylococcus aureus (MRSA) was confined to hospital patients, but since the 1990s it has been infecting otherwise healthy people in settings such as schools and locker rooms. Researchers now report the discovery of MRSA in U.S. wastewater treatment plants (WWTPs), identifying another possible environmental reservoir for the bacteria [EHP 120(11):1551–1558; Rosenberg Goldstein et al.]. People shed MRSA from their nostrils and skin and in their feces, which makes wastewater a likely vector for the bacteria. Previous research had identified MRSA in Swedish WWTPs, but no studies had been conducted on U.S. facilities.

The researchers collected wastewater samples throughout the treatment process at two mid-Atlantic and two Midwestern WWTPs. MRSA, as well as pathogenic methicillin-susceptible Staphylococcus aureus (MSSA), were present at all four WWTPs, with MRSA detected in 50% of all samples and MSSA detected in 55%. Genetic testing of the MRSA isolates revealed traits common among exceptionally virulent community-acquired strains circulating in the United States. Most MRSA isolates and 29% of MSSA isolates showed resistance to two or more classes of antibiotics, including several that the U.S. Food and Drug Administration has specifically approved for treating MRSA infections.

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