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Polymyxin B protects horses against induced endotoxaemia in vivo.
Abstract: A safe, affordable and effective treatment for endotoxaemia in horses is needed in order to reduce the incidence of this potentially fatal condition. Objective: To evaluate the effect of polymyxin B (PMB) on signs of experimentally-induced endotoxaemia. Objective: PMB ameliorates the adverse effects of endotoxaemia without causing nephrotoxicity. Methods: Four groups of 6 healthy mature horses each received 20 ng endotoxin/kg bwt i.v. over 30 mins. Additionally, each group received one of the following i.v.; 5000 u PMB/kg bwt 30 mins before endotoxin infusion; 5000 u PMB/kg bwt 30 mins after endotoxin infusion; 1000 u PMB/kg bwt 30 mins prior to endotoxin infusion; or saline. Clinical response data and samples were collected to determine neutrophil count, serum tumour necrosis factor (TNF) activity, plasma thromboxane B2 concentration and urine gamma glutamyltranspeptidase (GGT) to creatinine ratio. Results: Treatment with PMB before or after administration of endotoxin significantly reduced fever, tachycardia and serum TNF, compared to horses receiving saline. The differences in response to endotoxin were greatest between horses that received saline vs. those that received 5000 u PMB/kg bwt prior to endotoxin. Urine GGT:creatinine did not change significantly. Conclusions: This study indicates that PMB may be a safe and effective treatment of endotoxaemia, even when administered after onset. Although nephrotoxicity was not demonstrated with this model, caution should be exercised when using PMB in azotaemic patients.
Publication Date: 2004-07-16 PubMed ID: 15253079DOI: 10.2746/0425164044868350Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Adverse Effects
- Antibiotics
- Clinical Pathology
- Clinical Study
- Clinical Symptoms
- Diagnosis
- Disease Diagnosis
- Disease Management
- Disease Treatment
- Endotoxin
- Equine Health
- Experimental Methods
- Horses
- Immune Response
- In Vivo
- Inflammation
- Pathophysiology
- Pharmacology
- Tumor Necrosis Factor
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study examines the efficacy of Polymyxin B (PMB) in treating endotoxaemia in horses, demonstrating its potential to reduce symptoms and adverse effects without causing further kidney toxicity.
Research Objectives and Methodology
The article focuses on determining the impact of Polymyxin B (PMB) on experimentally-induced endotoxaemia, an unhealthy condition in horses caused due to the presence of endotoxins in the blood, which could potentially be fatal. Scientists conducted the study on twenty-four healthy, adult horses. They were divided into four groups, each of which was subjected to an endotoxin injection proportionate to their weight. Along with the endotoxin, each group also received either saline or PMB at varying dosages, either half an hour before or after the endotoxin.
- The first group received 5000 u PMB/kg body weight 30 mins before the endotoxin infusion.
- The second group received 5000 u PMB/kg body weight 30 mins after the endotoxin infusion.
- The third group received 1000 u PMB/kg body weight 30 mins prior to the endotoxin infusion.
- The fourth group received saline.
Through this setup, researchers wanted to understand the variation in effects related to dosage as well as timing of PMB administration. The variables measured include neutrophil count, serum tumour necrosis factor (TNF) activity, plasma thromboxane B2 concentration and urine gamma glutamyltranspeptidase (GGT) to creatinine ratio.
Research Results
The study found that administering PMB either before or after endotoxin significantly decreased fever, rapid heart rate (tachycardia), and serum TNF levels, in comparison to horses that only received saline. It is noteworthy that the greatest differences in endotoxaemia responses were observed between horses that received saline and those that received the highest dosage of PMB prior to endotoxin infusion. Interestingly, the level of GGT to creatinine in urine didn’t show a significant change.
Conclusions
The conclusions drawn from the study suggest that PMB could serve as an effective and safe treatment for endotoxaemia in horses, even when administered after the onset of the condition. The study did not show any evidence of nephrotoxicity (toxicity in the kidneys) in the PMB model, but it still advises caution when using PMB in azotaemic (elevated levels of nitrogen compounds in blood) patients. The results contribute significantly to ongoing research into affordable treatments for endotoxaemia in horses.
Cite This Article
APA
Barton MH, Parviainen A, Norton N.
(2004).
Polymyxin B protects horses against induced endotoxaemia in vivo.
Equine Vet J, 36(5), 397-401.
https://doi.org/10.2746/0425164044868350 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA.
MeSH Terms
- Animals
- Anti-Bacterial Agents / therapeutic use
- Body Temperature / drug effects
- Dose-Response Relationship, Drug
- Drug Administration Schedule / veterinary
- Endotoxemia / blood
- Endotoxemia / drug therapy
- Endotoxemia / veterinary
- Endotoxins / administration & dosage
- Heart Rate / drug effects
- Horse Diseases / blood
- Horse Diseases / drug therapy
- Horses
- Polymyxin B / therapeutic use
- Random Allocation
- Tumor Necrosis Factor-alpha / analysis
Citations
This article has been cited 14 times.- van Spijk JN, Beckmann K, Wehrli Eser M, Stirn M, Steuer AE, Saleh L, Schoster A. Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses. Antibiotics (Basel) 2023 May 5;12(5).
- Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses. Animals (Basel) 2022 Oct 26;12(21).
- van Spijk JN, Beckmann K, Wehrli Eser M, Boxler M, Stirn M, Rhyner T, Kaelin D, Saleh L, Schoster A. Adverse effects of polymyxin B administration to healthy horses. J Vet Intern Med 2022 Jul;36(4):1525-1534.
- Ray M, Manjunath A, Halami PM. Prevalence of polymyxin resistance through the food chain, the global crisis. J Antibiot (Tokyo) 2022 Apr;75(4):185-198.
- Perez-Ecija A, Buzon-Cuevas A, Aguilera-Aguilera R, Gonzalez-De Cara CA, Mendoza FJ. Blood Storage Conditions Affect Hematological Analysis in Samples From Healthy Donkeys and Donkeys With Experimentally-Induced Endotoxemia. Front Vet Sci 2020;7:640.
- Bauquier J, Tudor E, Bailey S. Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses. J Vet Intern Med 2020 Sep;34(5):2109-2116.
- Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys. J Vet Intern Med 2020 Jul;34(4):1631-1641.
- Taylor S. A review of equine sepsis. Equine Vet Educ 2015 Feb;27(2):99-109.
- Parkinson NJ, Buechner-Maxwell VA, Witonsky SG, Pleasant RS, Werre SR, Ahmed SA. Characterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using Next-Generation Sequencing. PLoS One 2017;12(5):e0177664.
- Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Milk thistle extract and silymarin inhibit lipopolysaccharide induced lamellar separation of hoof explants in vitro. Toxins (Basel) 2014 Oct 6;6(10):2962-74.
- Romanowski EG, Young EK, Mumper SM, Yates KA, Wozniak RAF, Zegans ME, Shanks RMQ. Combination Therapy of Cefiderocol and Polymyxin B Against Pseudomonas aeruginosa Keratitis Isolates In Vitro. Transl Vis Sci Technol 2025 Nov 3;14(11):7.
- Mendoza FJ, Buzon-Cuevas A, Aguilera-Aguilera R, Gonzalez-De Cara CA, De Las Heras A, Perez-Ecija A. Hemodynamic Response to Lipopolysaccharide Infusion and Effect of Meloxicam Administration on Cardiac Function in Donkeys. Animals (Basel) 2024 Dec 18;14(24).
- Gomez DE, Kopper JJ, Byrne DP, Renaud DL, Schoster A, Dunkel B, Arroyo LG, Mykkanen A, Gilsenan WF, Pihl TH, Lopez-Navarro G, Tennent-Brown BS, Hostnik LD, Mora-Pereira M, Marques F, Gold JR, DeNotta SL, Desjardins I, Stewart AJ, Kuroda T, Schaefer E, Oliver-Espinosa OJ, Agne GF, Uberti B, Veiras P, Delph Miller KM, Gialleti R, John E, Toribio RE. Treatment approaches to horses with acute diarrhea admitted to referral institutions: A multicenter retrospective study. PLoS One 2024;19(11):e0313783.
- Sharp CR, DeClue AE, Haak CE, Honaker AR, Reinero CR. Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of endotoxemia. J Feline Med Surg 2010 Apr;12(4):278-85.
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