scholarly journals Igm-enriched polyclonal immunoglobulins in an experimental model of gram negative pneumonia developing septic shock

2015 ◽  
Vol 3 (S1) ◽  
Author(s):  
R Vaschetto ◽  
N Clemente ◽  
A Pagni ◽  
T Esposito ◽  
F Mercalli ◽  
...  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takehiro Hashimoto ◽  
Ryuichi Takenaka ◽  
Haruka Fukuda ◽  
Kazuhiko Hashinaga ◽  
Shin-ichi Nureki ◽  
...  

Abstract Background Yersinia pseudotuberculosis infection can occur in an immunocompromised host. Although rare, bacteremia due to Y. pseudotuberculosis may also occur in immunocompetent hosts. The prognosis and therapeutic strategy, especially for immunocompetent patients with Y. pseudotuberculosis bacteremia, however, remains unknown. Case presentation A 38-year-old Japanese man with a mood disorder presented to our hospital with fever and diarrhea. Chest computed tomography revealed consolidation in the right upper lobe with air bronchograms. He was diagnosed with pneumonia, and treatment with intravenous ceftriaxone and azithromycin was initiated. The ceftriaxone was replaced with doripenem and the azithromycin was discontinued following the detection of Gram-negative rod bacteria in 2 sets of blood culture tests. The isolated Gram-negative rod bacteria were confirmed to be Y. pseudotuberculosis. Thereafter, he developed septic shock. Doripenem was switched to cefmetazole, which was continued for 14 days. He recovered without relapse. Conclusions We herein report a case of septic shock due to Y. pseudotuberculosis infection in an adult immunocompetent patient. The appropriate microorganism tests and antibiotic therapy are necessary to treat patients with Y. pseudotuberculosis bacteremia.


2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  

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.


Author(s):  
Mariana Chumbita ◽  
Pedro Puerta-Alcalde ◽  
Carlota Gudiol ◽  
Nicole Garcia-Pouton ◽  
Júlia Laporte-Amargós ◽  
...  

Objectives: We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. Methods: Multicenter retrospective study (2010-2019) of two prospective cohorts comparing BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Results: Of 1563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% vs 15%, p<0.001). Gram-negative bacilli caused 81% of episodes with septic shock; gram-positive cocci, 22%; and Candida species 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% vs 51%, p=0.002). Age >70 years (OR 2.3, 95% CI 1.2-4.7), IEAT for Candida spp. or gram-negative bacilli (OR 3.8, 1.3-11.1), acute kidney injury (OR 2.6, 1.4-4.9) and amikacin as the only active antibiotic (OR 15.2, 1.7-134.5) were independent risk factors for mortality, while combination of β-lactam and amikacin was protective (OR 0.32, 0.18-0.57). Conclusions: Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.


2019 ◽  
Vol 67 (1) ◽  
pp. 169-170
Author(s):  
Paola Andrea Yasnó-Navia ◽  
Luisa Fernanda Zuñiga-Ceron ◽  
Jhan Sebastián Saavedra-Torres ◽  
María Virginia Pinzón-Fernández

Gram-negative bacilli and cocci bacteria produce and release endotoxins, which are lipopolysaccharides found in the outer membrane of the cell wall. These endotoxins are responsible for releasing a series of inflammatory mediators such as IL1, TNFα and proteases, as well as lipid mediators such as prostaglandins, leukotrienes, thromboxanes and platelet-activating factor, ultimately activitating immune response cells like leukocytes, macrophages and platelets. These cells amplify the response to shock, generate a procoagulant state and produce alterations at the cellular level, for example, damage to the endothelium, which in the end benefit and worsen the state of septic shock (Figure 1).


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Sitthi Sukauichai ◽  
Chantana Pattarowas

Melioidosis is a bacterial infection, caused by Gram-negative bacillus, Burkholderia pseudomallei, widespread in Southeast Asia and the northern part of Australia, resulting in a high mortality rate in severe infection. However, it has rarely been reported in patients with chemotherapy-induced neutropenia. The authors described a case of melioidosis in a neutropenic patient presenting with septic shock after receiving chemotherapy. Blood and urine cultures were positive for Burkholderia pseudomallei, and CT scan showed multiple pulmonary nodules and hepatosplenic abscesses. The patient was successfully treated with antibiotics for the infection and with combined modalities for a malignancy.


2019 ◽  
Vol 20 (19) ◽  
pp. 4895 ◽  
Author(s):  
Mihee Jang ◽  
Jieun Kim ◽  
Yujin Choi ◽  
JeongKyu Bang ◽  
Yangmee Kim

Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis.


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