Treatment of endotoxaemia and septicaemia in the equine patient

Abstract

Endotoxins, constituents of the cell wall of gram-positive and gram-negative bacteria, regularly result in severe illness and death in horses. In endotoxaemia, these constituents are present in the systemic circulation; in septicaemia, whole microbes invade normally sterile parts of the body. Interaction of these endotoxins with pathogen recognition receptors leads to an inflammatory response that cannot always be sufficiently contained and hence needs direct treatment. Over the last decennia, our understanding of the pathophysiology of endotoxaemia and septicaemia has significantly increased. Based on improved understanding of the interaction between receptors and endotoxins as well as the subsequent downstream signalling pathways, new therapeutic targets have been identified in laboratory animal species and humans. Important species differences in the recognition of endotoxins and pathogens by their receptors as well as the inflammatory response to receptor activation hamper extrapolation of this information to the horse (and other species). Historically, horses with endotoxaemia and septicaemia have been treated mainly symptomatically and supportively. Based on the identified therapeutic targets, this review describes the current knowledge of the treatment for endotoxaemia and septicaemia in the horse with reference to the findings in other animal species and humans.

Antimicrobial resistance in clinical bacterial isolates from horses in the UK

“…Additionally, although polymyxin B may be used in horses as part of treatment of systemic inflammatory response syndrome (SIRS), it is used at an anti-endotoxic dose rate and not at an antimicrobial dose rate. The recommended dose for polymyxin B in the treatment of SIRS in horses is 6,000 iu/kg IV every 8 to 12 hours although the dose range varies between 5,000 -10,000 iu/kg [23][24][25][26]. The antimicrobial dose is higher (20,000 iu/kg), although neurotoxic and nephrotoxic effects have been seen at this dose [27,28] hence should not be used in horses.…”

Peroxidase-Mimicking Nanoassembly Mitigates Lipopolysaccharide-Induced Endotoxemia and Cognitive Damage in the Brain by Impeding Inflammatory Signaling in Macrophages

“…In humans, sepsis is a critically dangerous condition caused by infectious bacteria continuously releasing endotoxins into the blood. LPS-induced endotoxemia is one of the crucial factors responsible for the pathogenesis of sepsis. − H 2 O 2 , a toxic ROS, plays a dominant role in LPS/TLR4-mediated activation of the pro-inflammatory NF-κB signaling , cascade via HIF-1α − and simulates secretion of various pro-inflammatory markers such as TNFα, , IL-6, COX-2, HMGB1, and IL-1β, which mediate the pathophysiology of sepsis . We hypothesized that minimizing the levels of H 2 O 2 in pro-inflammatory cells would have beneficial effects on the regulation of LPS-induced endotoxemia.…”

Evaluation of tissue trauma and healing on the basis of tumour necrosis factor-alpha, interleukin-6, and C-reactive protein in peripheral blood during and after pyometra in bitches

“…The safest and most effective treatment for pyometra is OVH (12), although surgery is also associated with various degrees of inflammation. Thus, corticosteroids, antiinflammatory agents, anti-endotoxine antibodies and anti-cytokine therapies have been evaluated in humans and some animal species (17,19,26,28). According to our results, it would be beneficial to develop a cytokine-or toxin-targeting drug to support treatment of canine pyometra.…”