High-dose recombinant endotoxin neutralizing protein improves survival in rabbits with Escherichia coli sepsis
| Autor: | Thomas J. Novitsky, Gary R. Fleisher, Felicia Sattler, Anne M. Stack, Richard A. Saladino, George R. Siber, Claudette M. Thompson |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
Male Invertebrate Hormones medicine.medical_treatment Peritonitis Pharmacology Critical Care and Intensive Care Medicine Arthropod Proteins Sepsis Anti-Infective Agents Horseshoe Crabs medicine Animals Saline Escherichia coli Infections Acidosis Tumor Necrosis Factor-alpha business.industry medicine.disease Recombinant Proteins Endotoxins Bacteremia Immunology Ceftriaxone Gentamicin Tumor necrosis factor alpha Rabbits medicine.symptom business Antimicrobial Cationic Peptides medicine.drug |
| Zdroj: | Critical Care Medicine. 24:1203-1207 |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/00003246-199607000-00023 |
| Popis: | Objective To assess the benefit of a recombinant endotoxin neutralizing protein from Limulus polyphemus in treating Gram-negative bacterial sepsis in rabbits. Design Prospective, blinded, controlled, laboratory trial. Setting Animal research laboratory. Subjects New Zealand White rabbits. Interventions We established a rabbit model of Escherichia coli peritonitis and bacteremia, with high mortality rate, despite treatment with gentamicin and ceftriaxone. Twenty-five pairs of male New Zealand White rabbits were challenged intraperitoneally with E. coli O18ac K1 in 5% porcine mucin (mean 7 times 109 colony-forming units). All animals were treated with intravenous gentamicin (2.5 mg/kg) and ceftriaxone (100 mg/kg), and with either intravenous endotoxin neutralizing protein (50 mg/kg) or saline 1 hr after E. coli challenge. Measurements and Main Results All animals were bacteremic 1 hr after challenge (mean 3.6 times 105 colony-forming units/mL). Animals in both groups developed tachycardia, hypotension, and acidosis (NS). Geometric mean serum endotoxin and tumor necrosis factor (TNF) concentrations were significantly (p less than .001) higher 1 hr after challenge compared with baseline prechallenge concentrations in both groups. From 1 to 2 hrs after challenge, endotoxin concentrations increased 2.5-fold in control animals (95% confidence interval equals 13.1 to 32.9 endotoxin units/mL, p equals .024), whereas endotoxin concentrations increased only 1.2-fold in endotoxin neutralizing protein-treated animals (95% confidence interval equals 20.4 to 23.8 endotoxin units/mL, NS). TNF concentrations increased significantly (p less than .001) in both groups from 1 to 2 hrs after challenge. Eighteen (72%) of 25 endotoxin neutralizing protein-treated animals vs. 11 (44%) of 25 controls survived 24 hrs (p equals .032). Conclusions Treatment with endotoxin neutralizing protein had the following effects: a) the increase in serum endotoxin was blunted, but not TNF concentrations measured 1 hr after antibiotic treatment; and b) survival in rabbits with E. coli sepsis was improved. |
| Databáze: | OpenAIRE |
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