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

2013 ◽  
Vol 109 (04) ◽  
pp. 684-695 ◽  
Author(s):  
Adriana Vieira de Abreu ◽  
Jeffrey T. Holloway ◽  
James E. Marvin ◽  
Bjoern F. Kraemer ◽  
Guy A. Zimmerman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inflammatory Responses ◽  
Antibiotic Administration ◽  
Dependent Manner ◽  
Methicillin Resistant ◽  
Human Whole Blood ◽  
Cytokine Synthesis

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.

Infected pulmonary aneurysm following pulmonary artery banding

2016 ◽  
Vol 25 (9) ◽  
pp. 642-644
Author(s):  
Yuki Nakayama ◽  
Yusuke Iwata ◽  
Toshihide Nishimori ◽  
Takamasa Takeuchi
Keyword(s):  
Staphylococcus Aureus ◽  
Pulmonary Artery ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Pulmonary Stenosis ◽  
Pulmonary Artery Banding ◽  
Valvular Regurgitation ◽  
Antibiotic Administration ◽  
Foreign Material ◽  
Atrioventricular Canal ◽  
Methicillin Resistant

A 1-month-old girl, diagnosed with a common atrioventricular canal, moderate atrioventricular valvular regurgitation, and pulmonary hypertension, underwent pulmonary artery banding. Postoperatively, methicillin-resistant Staphylococcus aureus wound infection was treated with antibiotics. One month later, emergency surgery was performed for oozing rupture of an infected pulmonary aneurysm. The pulmonary aneurysm was completely resected, the banding tape was removed, and pulmonary angioplasty was performed to create pulmonary stenosis without using foreign material. Methicillin-resistant Staphylococcus aureus was cultured from the resected tissues and banding tape. The patient was discharged after antibiotic administration. Correction was performed at 1 year of age, and she remains well.

scholarly journals Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus.

1997 ◽  
Vol 41 (10) ◽  
pp. 2278-2281 ◽  
Author(s):  
R Nagano ◽  
K Shibata ◽  
T Naito ◽  
A Fuse ◽  
K Asano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Efficacy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Infection Model ◽  
Dependent Manner ◽  
Methicillin Resistant ◽  
Mrsa Strains ◽  
Systemic Infections

The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg/kg for vancomycin; and >200, >200, and 15.9 mg/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P < 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem.

scholarly journals Antibacterial Activity and Mode of Action of Lactoquinomycin A from Streptomyces bacillaris

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 7
Author(s):  
Beomkoo Chung ◽  
Oh-Seok Kwon ◽  
Jongheon Shin ◽  
Ki-Bong Oh
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Damage ◽  
Inhibitory Activity ◽  
Mode Of Action ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Dependent Manner ◽  
Mobility Shift ◽  
Concentration Dependent Manner ◽  
Methicillin Resistant

This study aims to isolate and identify the structure of antibacterial compounds having potent activity on methicillin-resistant Staphylococcus aureus (MRSA) from marine actinomycetes, and also to identify their mode of action. Lactoquinomycin A (LQM-A) (compound 1) and its derivatives (2–4) were isolated from marine-derived Streptomyces bacillaris strain MBTC38, and their structures were determined using extensive spectroscopic methods. These compounds showed potent antibacterial activities against Gram-positive bacteria, with MIC values of 0.06–4 μg/mL. However, the tested compounds exhibited weak inhibitory activity against Gram-negative bacteria, although they were effective against Salmonella enterica (MIC = 0.03–1 μg/mL). LQM-A exhibited the most significant inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC = 0.25–0.5 μg/mL), with a low incidence of resistance. An in vivo dual-reporter assay designed to distinguish between compounds that inhibit translation and those that induce DNA damage was employed to assess the mode of action of LQM-A. LQM-A-induced DNA damage and did not inhibit protein synthesis. The gel mobility shift assay showed that LQM-A switched plasmid DNA from the supercoiled to relaxed form in a time- and concentration-dependent manner. These data suggest that LQM-A intercalated into double-stranded DNA and damaged DNA repair.

scholarly journals Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 9 (10) ◽  
pp. 2055
Author(s):  
Monika Kumaraswamy ◽  
Kamilla Wiull ◽  
Bishnu Joshi ◽  
George Sakoulas ◽  
Armin Kousha ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Whole Blood ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Ex Vivo ◽  
Membrane Vesicles ◽  
World Health ◽  
Human Neutrophils ◽  
Methicillin Resistant

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures.

scholarly journals Thymol Inhibits Biofilm Formation, Eliminates Pre-Existing Biofilms, and Enhances Clearance of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Mouse Peritoneal Implant Infection Model

2020 ◽  
Vol 8 (1) ◽  
pp. 99 ◽  
Author(s):  
Zhongwei Yuan ◽  
Yuyun Dai ◽  
Ping Ouyang ◽  
Tayyab Rehman ◽  
Sajjad Hussain ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inflammatory Responses ◽  
Extracellular Dna ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Mouse Infection Model ◽  
Cell Counts ◽  
First Choice

Methicillin-resistant Staphylococcus aureus (MRSA) is a common human pathogen that causes several difficult-to-treat infections, including biofilm-associated infections. The biofilm-forming ability of S. aureus plays a pivotal role in its resistance to most currently available antibiotics, including vancomycin, which is the first-choice drug for treating MRSA infections. In this study, the ability of thymol (a monoterpenoid phenol isolated from plants) to inhibit biofilm formation and to eliminate mature biofilms, was assessed. We found that thymol could inhibit biofilm formation and remove mature biofilms by inhibiting the production of polysaccharide intracellular adhesin (PIA) and the release of extracellular DNA (eDNA). However, cotreatment with thymol and vancomycin was more effective at eliminating MRSA biofilms, in a mouse infection model, than monotherapy with vancomycin. Comparative histopathological analyses revealed that thymol reduced the pathological changes and inflammatory responses in the wounds. Assessments of white blood cell counts and serum TNF-α and IL-6 levels showed reduced inflammation and an increased immune response following treatment with thymol and vancomycin. These results indicate that combinatorial treatment with thymol and vancomycin has the potential to serve as a more effective therapy for MRSA biofilm-associated infections than vancomycin monotherapy.

scholarly journals Recalcitrant methicillin-resistant Staphylococcus aureus infection of bone cells: Intracellular penetration and control strategies

2020 ◽  
Vol 9 (2) ◽  
pp. 49-59
Author(s):  
Kristin Yu ◽  
Lee Song ◽  
Hyunwoo Paco Kang ◽  
Hyuk-Kwon Kwon ◽  
Jungho Back ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bone Cells ◽  
Time Lapse ◽  
Antibiotic Administration ◽  
Protective Effects ◽  
Bacterial Colony ◽  
Methicillin Resistant ◽  
Surgical Preparation

Aims To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. Methods Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. Results MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. Conclusion The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. Cite this article: Bone Joint Res. 2020;9(2):49–59.

Sign in / Sign up

Export Citation Format

Share Document