scholarly journals LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

2020 ◽  
Vol 61 (12) ◽  
pp. 1776-1783
Author(s):  
Auguste Dargent ◽  
Jean-Paul Pais de Barros ◽  
Samir Saheb ◽  
Randa Bittar ◽  
Wilfried Le Goff ◽  
...  
Keyword(s):  
Septic Shock ◽  
Free Form ◽  
Ldl Apheresis ◽  
Direct Hemoperfusion ◽  
Gram Negative ◽  
Improve Outcome ◽  
Gram Negative Bacteremia ◽  
Extracorporeal Removal ◽  
Prime Target

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

scholarly journals LDL-apheresis as an alternate method for plasma LPS purification in healthy volunteers, dyslipidemic and septic patients

2020 ◽  
Author(s):  
Auguste Dargent ◽  
Jean-Paul Pais de Barros ◽  
Samir Saheb ◽  
Randa Bittar ◽  
Wilfried Le Goff ◽  
...  
Keyword(s):  
Septic Shock ◽  
Polymyxin B ◽  
Low Density Lipoproteins ◽  
Free Form ◽  
Low Density ◽  
Ldl Apheresis ◽  
Gram Negative Bacteremia ◽  
Phosphate Buffered Saline ◽  
Prime Target

AbstractLipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. Extracorporeal removal method by polymyxin B hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including low density lipoproteins (LDL). Lipoproteins are critical for physiological LPS clearance, as LPS are carried by low density lipoproteins (LDL) to the liver for elimination. We hypothesized that LDL-apheresis can be an alternate method for LPS removal. We demonstrated first in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in phosphate-buffered saline. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL-apheresis for familial hypercholesterolemia is also removed during their LDL-apheresis sessions, both with electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

scholarly journals Interaction of Antimicrobial Peptide Temporin L with Lipopolysaccharide In Vitro and in Experimental Rat Models of Septic Shock Caused by Gram-Negative Bacteria

2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  
Keyword(s):  
Septic Shock ◽  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Amphibian Skin ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Rat Models ◽  
E Coli ◽  
Tnf Α

ABSTRACT Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used β-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and β-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-α levels, resulting in the highest survival rates.

scholarly journals 519. Multidrug-resistant Gram-Negative Bacteremia in Pediatric Patients: Is It Time to Change to Empiric Meropenem?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S250-S250
Author(s):  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach
Keyword(s):  
Antimicrobial Agents ◽  
Pediatric Patients ◽  
Multidrug Resistant ◽  
Suspected Sepsis ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Gram Negative Bacteremia ◽  
Delayed Initiation ◽  
Poor Outcomes

Abstract Background The rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients. Methods All episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results. Results A total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1. Conclusion In our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.

scholarly journals Analysis of Endotoxin Adsorption in Two Swedish Patients with Septic Shock

2019 ◽  
Vol 47 (Suppl. 3) ◽  
pp. 51-53 ◽  
Author(s):  
Marcus Ewert Broman ◽  
Mikael Bodelsson
Keyword(s):  
Septic Shock ◽  
Adsorption Process ◽  
Case Series ◽  
Gram Negative ◽  
Blood Compartment ◽  
Lipopolysaccharide Endotoxin ◽  
Infectious Focus ◽  
Positively Charged

Background: Lipopolysaccharide (endotoxin) from the outer Gram-negative bacterial wall can induce a harmful immunologic response, involving hemodynamic deprivation, and is one important motor driving the septic cascade. The positively charged poly-imine ethylene layer on the oXiris membrane is capable of adsorbing negatively charged endotoxin molecules and removing them from the blood compartment. Endotoxin is detrimental and should be removed from blood. Summary: The adsorbable endotoxin fraction in blood arises from a tight balance between seeding from an infectious focus and removal by an overwhelmed immune system. The net sum of remaining endotoxin in blood is available for an adsorption process in the oXiris filter. Endotoxin data from 2 patients with severe Gram-negative septic shock and endotoxemia in this case series, speaks for a considerable share of the adsorption of the oXiris filter in the endotoxin net removal over time. Key Messages: Analysis of combined in vitro and in vivo data speaks for an effect of the oXiris filter in lowering endotoxin.

Treatment of Pyonephritis Complicated by Septic Shock Using Extracorporeal Device Polymyxin B-Hemoperfusion

2020 ◽  
Vol 49 (5) ◽  
pp. 627-630
Author(s):  
Gabriele Amoruso ◽  
Nicola Di Venosa ◽  
Luigi Rizzi ◽  
Gianna Lupo ◽  
Armando Gisotti ◽  
...  
Keyword(s):  
Septic Shock ◽  
Treatment Method ◽  
Polymyxin B ◽  
Surviving Sepsis Campaign ◽  
Direct Hemoperfusion ◽  
Gram Negative ◽  
Polymyxin B Hemoperfusion ◽  
Established Treatment

Direct hemoperfusion using polymyxin B-immobilized fiber (PMX-DHP) is an established treatment method for septic shock caused by Gram-negative infections. We report one instance in which PMX-DHP therapy has been used successfully in a 33-year-old woman with septic shock from urosepsis. Although there is lack of recommendations in latest Surviving Sepsis Campaign Guidelines, evidence of PMX-DHP efficacy in this subset of patients is growing.

scholarly journals Clinical and Microbiological Outcomes in Obese Patients Receiving Colistin for Carbapenem-Resistant Gram-Negative Bloodstream Infection

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Simon W. Lam ◽  
Vasilios Athans
Keyword(s):  
Length Of Hospital Stay ◽  
Ideal Body Weight ◽  
Secondary Outcome ◽  
Obese Patients ◽  
International Consensus ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Gram Negative Bacteremia ◽  
Cure Rates

ABSTRACT Carbapenem-resistant infections are associated with poor outcomes, and treatment options are limited. Colistin is one of few antibiotics which retain in vitro activity against carbapenem-resistant pathogens. However, despite the availability of international consensus guidelines for the dosing of polymyxins, there are limited data on the effects of dosing on clinical outcomes among obese patients with carbapenem-resistant Gram-negative bacteremia. This retrospective study evaluated whether obesity was associated with day 7 global cure rates among patients with carbapenem-resistant Gram-negative bacteremia who were treated with an ideal body weight (IBW)-based colistin dosing regimen. Secondary outcomes included microbiological cure, clinical cure, length of hospital stay, in-hospital mortality, and day 7 acute kidney injury. After screening to identify 167 patients, 77 (46.1%) and 90 (53.9%) were classified as obese and nonobese, respectively. Patient characteristics were well balanced at baseline, except that obese patients were more often female and received a higher daily dose per IBW (3.7 versus 2.9 mg/kg/day, P = 0.03). Global cure rates were similar between groups (44.2% for obese versus 55.6% for nonobese, P = 0.14). After adjusting for baseline differences, obesity was not a significant predictor of global cure (adjusted odds ratio [AOR], 0.59; 95% confidence interval [CI], 0.31 to 1.11; P = 0.10). Obesity was associated with a lower likelihood of microbiological clearance (72.7% versus 91.1%, P = 0.02). No other secondary outcome differences were observed, though each outcome was numerically worse among obese patients. Obesity was not associated with differences in global cure rates. However, the difference in microbiological clearance warrants further investigation.

scholarly journals Synergistic effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in treatment of rabbit gram-negative sepsis.

1996 ◽  
Vol 40 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Y Lin ◽  
W J Leach ◽  
W S Ammons
Keyword(s):  
Escherichia Coli ◽  
Septic Shock ◽  
Combined Treatment ◽  
Bacterial Clearance ◽  
Gram Negative ◽  
E Coli ◽  
Terminal Fragment ◽  
Cephalosporin Antibiotic

As a consequence of their bactericidal actions, many antibiotics cause the release of endotoxin, a primary mediator of gram-negative sepsis. Bactericidal/permeability-increasing protein (BPI) has bactericidal activity and neutralizes endotoxin in vitro and in vivo. We sought to examine the effect of a recombinant N-terminal fragment of BPI (rBPI21) in conjunction with cefamandole, a cephalosporin antibiotic, in the treatment of Escherichia coli bacteremia and septic shock in rabbits. Cefamandole (100 mg/kg of body weight) was injected intravenously. This was followed by simultaneous 10-min infusions of E. coli O7:K1 (9 x 10(9) CFU/kg) and rBPI21 (10 mg/kg). rBPI21 was continuously infused for an additional 110 min at 10 mg/kg/h. The administration of rBPI21 in conjunction with the administration of cefamandole prevented the cefamandole-induced increase of free endotoxin in plasma, accelerated bacterial clearance, ameliorated cardiopulmonary dysfunction, and thereby, prevented death, whereas neither agent alone was protective in this animal model. The efficacy of the combined treatment with rBPI21 and cefamandole suggests a synergistic interaction between the two agents. The data indicate that rBPI21 may be useful in conjunction with traditional antibiotic therapy.

#15: Risk Factors of Infection related mortality in Pediatric Acute Myeloid Leukemia- Single Institute Experience: 2016–2018

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S1-S1
Author(s):  
Ahmed Bayoumi
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Infectious Complications ◽  
P Value ◽  
Gram Negative ◽  
Gram Negative Bacteremia ◽  
Febrile Episodes ◽  
Acute Myeloid

Abstract Children with acute myeloid leukemia (AML) are at a particularly high risk for infectious complications related to the highly intensive chemotherapy. Infections leads to mortality and prolong hospitalization. The aim of the study is to evaluate the risk factors, infectious complications and assess outcome of febrile episodes during induction and consolidation chemotherapy courses in children with AML at the Pediatric Oncology Department, National Cancer Institute, Cairo University from January 2016 to December 2018. Infectious complications were evaluated retrospectively in 621 febrile episodes. Mortality from gram negative bacteremia was 29.9%, in febrile episodes with multidrug resistant gram negative bacteremia: Mortality was 39.2 % in febrile episodes with multidrug resistant gram negative bacteremia and septic shock. Mortality was 71.8 % (p value <0.001). Mortality was high in early chemotherapy phase (intensive timing). Infection related mortality was 39%. In our institute there is epidemiological shift towards gram negative organisms. Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of pediatric Acute myeloid leukemia. It is Important to trace the risk factors that may affect the outcome of febrile episodes. Summary of Significant laboratory and clinical predictors of mortality Risk Factor Mortality p value Septic shock 55% <0.001 Septic shock with MDRO 72% Cardiac impairment/inotropic support 65.60% Presence Of Central venous line 18.30% Episode duration >18 days 20.50% Start of antimicrobial in relation to start of chemotherapy < 16 days 33% Episodes: Not in remission 15.60% Risk factor Mortality p value CRP more than or equals 90 mg/l 24.4% Not significant ANC LESS THAN 500 29.9% 0.003 Hgb less than or equals to 7 g/dl 19.9% 0.633 Platelets less than 20000/cc 29.9% 0.299 Liver impairment (grades 3 and 4) 42.2% 0.025 Electrolyte imbalance (grades 3 and 4) 24.1% 0.003 Renal impairment 56.8% 0.025 Coagulopathy 41% <0.001

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