The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death

Exosomes play a crucial role in the progression of infectious diseases, as exosome release and biogenesis are affected by external factors, such as pathogenic infections. Pyrogens may aide in the progression of diseases by triggering inflammation, endothelial cell injury, and arterial plaque rupture, all of which can lead to acute coronary disease, resulting in cardiac tissue death and the onset of a cardiac event (CE). To better understand the effects of Gram-negative bacterial infections on exosome composition and biogenesis, we examined exosome characteristics after treatment of AC16 human cardiomyocytes with lipopolysaccharide (LPS), which served as a model system for Gram-negative bacterial infection. Using increasing doses (0, 0.1, 1, or 10 µg) of LPS, we showed that treatment with LPS substantially altered the composition of AC16-derived exosomes. Both the relative size and the quantity (particles/mL) of exosomes were decreased significantly at all tested concentrations of LPS treatment compared to the untreated group. In addition, LPS administration reduced the expression of exosomal proteins that are related to exosomal biogenesis. Conversely, we observed an increase in immunomodulators present after LPS administration. This evaluation of the impact of LPS on cardiac cell death and exosome composition will yield new insight into the importance of exosomes in a variety of physiological and pathological processes as it relates to disease progression, diagnosis, and treatment.

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Clinical Outcomes and Healthcare Utilization Related to Multidrug-Resistant Gram-Negative Infections in Community Hospitals

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2016.230 ◽

2016 ◽

Vol 38 (1) ◽

pp. 31-38 ◽

Cited By ~ 1

Author(s):

Kristen V. Dicks ◽

Deverick J. Anderson ◽

Arthur W. Baker ◽

Daniel J. Sexton ◽

Sarah S. Lewis

Keyword(s):

Bacterial Infections ◽

Multidrug Resistant ◽

Healthcare Resource Utilization ◽

Community Hospitals ◽

Readmission Rates ◽

Gram Negative ◽

Mortality Difference ◽

Tract Infections ◽

Multivariable Regression Models ◽

The Impact

OBJECTIVETo evaluate the impact of multidrug-resistant gram-negative rod (MDR-GNR) infections on mortality and healthcare resource utilization in community hospitals.DESIGNTwo matched case-control analyses.SETTINGSix community hospitals participating in the Duke Infection Control Outreach Network from January 1, 2010, through December 31, 2012.PARTICIPANTSAdult patients admitted to study hospitals during the study period.METHODSPatients with MDR-GNR bloodstream and urinary tract infections were compared with 2 groups: (1) patients with infections due to nonMDR-GNR and (2) control patients representative of the nonpsychiatric, non-obstetric hospitalized population. Four outcomes were assessed: mortality, direct cost of hospitalization, length of stay, and 30-day readmission rates. Multivariable regression models were created to estimate the effect of MDR status on each outcome measure.RESULTSNo mortality difference was seen in either analysis. Patients with MDR-GNR infections had 2.03 higher odds of 30-day readmission compared with patients with nonMDR-GNR infections (95% CI, 1.04–3.97, P=.04). There was no difference in hospital direct costs between patients with MDR-GNR infections and patients with nonMDR-GNR infections. Hospitalizations for patients with MDR-GNR infections cost $5,320.03 more (95% CI, $2,366.02–$8,274.05, P<.001) and resulted in 3.40 extra hospital days (95% CI, 1.41–5.40, P<.001) than hospitalizations for control patients.CONCLUSIONSOur study provides novel data regarding the clinical and financial impact of MDR gram-negative bacterial infections in community hospitals. There was no difference in mortality between patients with MDR-GNR infections and patients with nonMDR-GNR infections or control patients.Infect Control Hosp Epidemiol 2016;1–8

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Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01130-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zaihui Peng ◽

Xiaochun Zhang ◽

Long Yuan ◽

Ting Li ◽

Yajie Chen ◽

...

Keyword(s):

Wound Healing ◽

Bacterial Infections ◽

Antibacterial Properties ◽

Platelet Membrane ◽

Gram Negative Bacteria ◽

Gram Negative ◽

The Impact ◽

Copper Silicate

AbstractSerious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents. Graphical Abstract

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1575. Predictors of Negative Clinical Outcomes among Patients treated with Meropenem-Vaborbactam for Serious Gram-Negative Bacterial Infections: Impact of Delayed Appropriate Antibiotic Selection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1755 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S786-S786

Author(s):

Sara Alosaimy ◽

Abdalhamid M Lagnf ◽

Sarah Jorgensen ◽

Travis J Carlson ◽

Jinhee Jo ◽

...

Keyword(s):

Regression Analysis ◽

Antibiotic Therapy ◽

Clinical Outcomes ◽

Bacterial Infections ◽

The United States ◽

Research Support ◽

Gram Negative ◽

Appropriate Therapy ◽

Tract Infections ◽

The Impact

Abstract Background Numerous number of studies have found a positive correlation between delayed appropriate antibiotic therapy and negative clinical outcomes (NCO) in Gram-negative bacterial infections (GNBI). The combination of meropenem with vaborbactam (MVB) received Food and Drug Administration approval for the treatment of complicated urinary tract infections and acute pyelonephritis caused by susceptible organisms in August 2017. We sought to determine the impact of delayed appropriate therapy with MVB on NCO among patients with GNBI. Methods Multi-center, retrospective cohort study from October 2017 to March 2020. We included adult patients treated with MVB for >72 hours. We excluded patients who received alternative appropriate antibiotics for GNB prior to MVB and patients with unknown dates for index culture. NCO were defined as 30-day mortality and/or microbiological recurrence. All outcomes were measured from MVB start date. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineates the risk of NCO. Multivariable logistic regression analysis (MLR) was used to examine the independent association between the CART-derived-BP and NCO. Variables were retained in the model if P< 0.2 and removed in a backward stepwise approach. Results A total of 86 patients were included from 13 institutions in the United States: median(IQR) age 55 (37-67) years, 67% male, and 48% Caucasian. Median(IQR) APACHE II and Charlson Comorbidity index scores were 18(11-26) and 4(2-6), respectively. Common sources of infection were respiratory (37%) and intra-abdominal (21%). The most common pathogens were carbapenem-resistant Enterobacterales (83%). CART-derived BP between early and delayed treatment was 48 hours, where NCO was increased (36% vs.7%; P=0.04). Delayed MVB initiation was independently associated with NCO in the MLR (aOR=7.4, P=0.02). Results of Regression Analysis of Variables Associated With Negative Clinical Outcomes and Delayed Appropriate Therapy with Meropenem-vaborbactam Conclusion Our results suggest that delaying appropriate antibiotic therapy with MVB for >48 hours significantly increases the risk of NCO in patients with GNBI. Clinicians must ensure timely administration of MVB to assure best outcomes in patients with GNBI. Disclosures Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

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Integrated Endotoxin-Adsorption and Antibacterial Properties of Platelet-Membrane-Coated Copper Silicate Hollow Microspheres for Wound Healing

10.21203/rs.3.rs-903043/v1 ◽

2021 ◽

Author(s):

Zaihui Peng ◽

Xiaochun Zhang ◽

Long Yuan ◽

Yajie Chen ◽

Ting Li ◽

...

Keyword(s):

Wound Healing ◽

Bacterial Infections ◽

Antibacterial Properties ◽

Platelet Membrane ◽

Gram Negative Bacteria ◽

Gram Negative ◽

The Impact ◽

Copper Silicate

Abstract Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bactericidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

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The rise and rise of antimicrobial resistance in Gram-negative bacteria

Microbiology Australia ◽

10.1071/ma19018 ◽

2019 ◽

Vol 40 (2) ◽

pp. 62

Author(s):

Adam Stewart ◽

Hugh Wright ◽

Krispin Hajkowicz

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

New Drugs ◽

Resistant Bacteria ◽

Drug Resistant ◽

International Consensus ◽

Gram Negative ◽

Mortality And Morbidity ◽

Inappropriate Use ◽

The Impact

Antimicrobial resistance is a major threat to the delivery of effective care and already causes 700000 excess deaths per year worldwide. International consensus on action to combat antimicrobial resistance was reached in 2015. Australia is implementing a national strategy. The clinical consequences of antimicrobial resistance are seen most acutely in multi-drug resistant Gram-negative bacterial infections, where they cause increased mortality and morbidity and threaten the delivery of once routine medical care. The solution to antimicrobial resistance is complex and multifaceted. Antimicrobial stewardship, that is optimising the use of the antibiotics we currently have, is the most rapidly deployable mitigation. Several novel antibiotics with activity against a range of drug-resistant bacteria are now available clinically, leading to hope that innovative solutions will reduce the impact of resistance. It is critical that these new drugs are protected from inappropriate use.

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