ICU treatment of sepsis and septic shock

2018 ◽  
Author(s):  
Matt Wise ◽  
Paul Frost
Keyword(s):  
Septic Shock ◽  
Elderly Population ◽  
Indwelling Catheters ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Patient Demographics ◽  
Dramatic Rise ◽  
Gram Negative Organisms ◽  
Sepsis And Septic Shock ◽  
Icu Treatment

Bacteria are the most frequent causes of severe sepsis and septic shock, while viruses, fungi, and parasites are implicated less often. Positive cultures are found in only 60% of cases; this may be the result of previous antibiotic therapy or inadequate sampling or testing. The etiology of sepsis is constantly changing; whereas Gram-negative organisms used to make up the majority of cases, Gram-positive bacteria now predominate. Sepsis due to fungal disease has also seen a dramatic rise. These changes may be explained by alterations in patient demographics, such as an increasingly elderly population with multiple comorbidities; an increased frequency of indwelling catheters or devices; and greater numbers of patients with immunosuppression as a result of disease or drug therapy. This chapter covers symptoms, demographics, diagnosis, investigation, prognosis, and treatment within the ITU environment.

scholarly journals Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum

2021 ◽  
Author(s):  
Erum Malik ◽  
David A. Phoenix ◽  
Timothy J. Snape ◽  
Frederick Harris ◽  
Jaipaul Singh ◽  
...  
Keyword(s):  
Helical Structure ◽  
Food Preservation ◽  
Forming Process ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria ◽  
Alkaline Conditions ◽  
Ph Dependent ◽  
Gram Negative Organisms

AbstractHere the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5–26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3–5.1 mN m−1) and lyse (↑ 15.1–32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1–23) in the N → C direction, with −  < µH > increasing overall from circa − 0.8 to − 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.

scholarly journals Outcomes in patients with gram-negative sepsis treated with gentamicin

2012 ◽  
Vol 3 (3) ◽  
pp. 109-113 ◽  
Author(s):  
Peter Pillans ◽  
Joel Iedema ◽  
Peter Donovan ◽  
Robert Newbery ◽  
Venetia Whitehead ◽  
...  
Keyword(s):  
Renal Function ◽  
Elderly Population ◽  
Total Body Weight ◽  
Therapeutic Drug ◽  
Gram Negative ◽  
Clinical Endpoints ◽  
Patient Demographics ◽  
Antimicrobial Sensitivity ◽  
Total Body ◽  
Baseline Renal Function

Objective: Recent changes to therapeutic drug monitoring (TDM) of gentamicin have been advocated in Australia. It remains uncertain whether these will have an effect on hard clinical endpoints. The aim of this study was to determine clinical outcomes in patients with gram-negative infections treated with gentamicin. Methods: Microbiology results of patients with confirmed gram-negative cultures were retrospectively reviewed and those treated with gentamicin included. Medical records were reviewed and patient demographics, diagnosis, renal function, comorbidities, gentamicin doses, duration, monitoring, concomitant antibiotics, antimicrobial sensitivity and clinical and microbiological outcomes recorded. Results: A total of 100 patients were included in the study: 52% were male, median age 64 years (17–97). Total body weight was recorded in 56% (median 74.5 kg, range 35–134 kg). Most patients had two or more important comorbidities. A total of 72% received empiric and 28% directed treatment. The organism was identified on blood culture in 45%, urine culture in 43% and aspiration of liver abscess in 12%; 95% of organisms were sensitive to gentamicin. Baseline renal function was normal in 62%. Mean gentamicin dose was 3.9 ± 0.9 mg/kg and mean duration 2.9 ± 2.5 days. Only 21% had optimal TDM. Clinical outcome was favourable in 90%. There were no cases of preventable serious toxicity. Conclusions: Despite the modest doses of gentamicin used in an elderly population with comorbidities, as well as the absence of optimal TDM, outcomes were favourable without preventable serious toxicity.

Fusobacterium nucleatum, the first Gram-negative bacterium demonstrated to produce polyglutamate

2009 ◽  
Vol 55 (5) ◽  
pp. 627-632 ◽  
Author(s):  
Thomas Candela ◽  
Marie Moya ◽  
Michel Haustant ◽  
Agnès Fouet
Keyword(s):  
In Silico Analysis ◽  
Fusobacterium Nucleatum ◽  
Gram Negative Bacteria ◽  
Negative Bacterium ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
The Third ◽  
Gram Negative Organisms ◽  
First Time

Poly-γ-glutamate has been described in many Gram-positive organisms. When anchored to the surface, it is a capsule and as such a virulence factor. Based on sequence similarities, few Gram-negative organisms have been suggested to synthesize poly-γ-glutamate. For the first time, a Gram-negative bacterium, Fusobacterium nucleatum , is shown to produce and secrete poly-γ-glutamate. Putative poly-γ-glutamate-synthesizing genes from Gram-negative organisms have been compared with their Gram-positive homologs by in silico analysis, i.e., gene sequence and phylogenetic analysis. Clusters of three instead of four genes were highlighted by our screen. The products of the first two genes display similarity with their Gram-positive equivalents, yet the sequences from the Gram-negative organisms can be distinguished from those of the Gram-positives. Interestingly, the sequence of the predicted product of the third gene is conserved among Gram-negative bacteria but displays no similarity to that of either the third or fourth gene of the Gram-positive operons. It is suggested that, like for Gram-positive bacteria, poly-γ-glutamate has a role in virulence for pathogens and one in survival for other Gram-negative bacteria.

Complement activation in septic shock due to gram-negative and gram-positive bacteria

1982 ◽  
Vol 10 (5) ◽  
pp. 305-307 ◽  
Author(s):  
CRISTÓBAL LEÓN ◽  
MARÍA J. RODRIGO ◽  
ANTONIO TOMASA ◽  
MARIA T. GALLART ◽  
FRANCISCO J. LATORRE ◽  
...  
Keyword(s):  
Septic Shock ◽  
Complement Activation ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

scholarly journals Secretory Phospholipase A2 Is the Principal Bactericide for Staphylococci and Other Gram-Positive Bacteria in Human Tears

1998 ◽  
Vol 66 (6) ◽  
pp. 2791-2797 ◽  
Author(s):  
Xiao-Dan Qu ◽  
Robert I. Lehrer
Keyword(s):  
Bactericidal Activity ◽  
Tear Film ◽  
Phospholipase A ◽  
Secretory Phospholipase A2 ◽  
Gram Positive ◽  
Gram Negative ◽  
Secretory Phospholipase ◽  
Calcium Dependent ◽  
Gram Positive Bacteria ◽  
Gram Negative Organisms

ABSTRACT We examined human tears for molecules that killed gram-positive bacteria. The principal mediator of bactericidal activity against staphylococci proved to be a calcium-dependent enzyme, secretory phospholipase A2. Whereas the concentration of secretory phospholipase A2 in the normal tear film exceeded 30 μg/ml, only 1.1 ng (<0.1 nM) of the enzyme per ml sufficed to killListeria monocytogenes and 15 to 80 ng/ml killedStaphylococcus aureus. Despite its efficacy against gram-positive bacteria, secretory phospholipase A2 lacked bactericidal activity against gram-negative organisms (Escherichia coli, Salmonella typhimurium, andPseudomonas aeruginosa) when tested in the ionic environment of tears. Given the presence of secretory phospholipase A2 in tears, intestinal secretions, and leukocytes, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against gram-positive bacteria.

Outcome of patients with sepsis and septic shock after ICU treatment

1998 ◽  
Vol 383 (1) ◽  
pp. 44-48 ◽  
Author(s):  
M. H. Schoenberg ◽  
M. Weiss ◽  
P. Radermacher
Keyword(s):  
Septic Shock ◽  
Sepsis And Septic Shock ◽  
Icu Treatment

scholarly journals Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock

2004 ◽  
Vol 72 (3) ◽  
pp. 1820-1823 ◽  
Author(s):  
Toshio Toyosawa ◽  
Mamoru Suzuki ◽  
Kohtarou Kodama ◽  
Seiichi Araki
Keyword(s):  
Septic Shock ◽  
Bacterial Infection ◽  
Intravenous Infusion ◽  
Sodium Phosphate ◽  
Therapeutic Strategy ◽  
Therapeutic Effects ◽  
Vitamin B2 ◽  
Gram Positive ◽  
Gram Negative ◽  
Sepsis And Septic Shock

ABSTRACT Highly purified vitamin B2 (riboflavin 5′-sodium phosphate; purity > 97%) treatment by intravenous infusion at doses above those used clinically to treat vitamin B2 deficiency showed therapeutic effects in mice not only in cases of endotoxin- and exotoxin-induced shock but also in cases of gram-negative and gram-positive bacterial infection even after the toxemia had already begun.

scholarly journals NKT Cells in Sepsis

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Briana Leung ◽  
Hobart W. Harris
Keyword(s):  
Septic Shock ◽  
T Cells ◽  
Immune Cells ◽  
Natural Killer T Cells ◽  
Nkt Cells ◽  
Innate And Adaptive Immunity ◽  
Gram Negative ◽  
Sepsis And Septic Shock ◽  
Killer T Cells

Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex proinflammatory cascades that include the activation of various immune cells and the exuberant secretion of proinflammatory cytokines by these cells. Natural killer T-cells (NKTs) are a sublineage of T cells that share characteristics of conventional T cells and NK cells and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation.

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