Related Experiment Videos
Effect of polymyxin B on experimental shock from meningococcal and Escherichia coli endotoxins
G Baldwin1, G Alpert, G L Caputo
1Department of Medicine, Children's Hospital, Boston, MA 02115.
Abstract:
Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P less than .05) and improved 24-h survival (P less than .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05). In vitro studies confirmed that PMB at 10 micrograms/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS.
Insights
Polymyxin B (PMB) did not improve survival in rabbits with meningococcal shock. However, PMB showed protective effects against E. coli lipopolysaccharide (LPS) induced shock, suggesting differential activity against bacterial toxins.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Meningococcemia is a leading cause of septic shock in children.
- Lipooligosaccharide (LOS) from Neisseria meningitidis is a key virulence factor in meningococcal disease.
- Polymyxin B (PMB) is an antibiotic with known endotoxin-neutralizing properties.
Purpose of the Study:
- To evaluate the efficacy of Polymyxin B (PMB) in improving survival from meningococcal shock.
- To compare PMB's protective activity against meningococcal lipooligosaccharide (LOS) with its activity against Escherichia coli lipopolysaccharide (LPS).
Main Methods:
- Rabbits were challenged with lethal doses (LD90) of meningococcal LOS or (LD80) of E. coli LPS.
- PMB was administered intravenously 30 minutes before challenge or premixed with the endotoxin in vitro.
- Hemodynamic parameters, serum bicarbonate, tumor necrosis factor (TNF) levels, and 24-hour survival were monitored.
Main Results:
- PMB administration before meningococcal LOS challenge did not significantly affect survival, heart rate, mean arterial pressure, serum bicarbonate, or TNF levels.
- Premixing PMB with meningococcal LOS in vitro improved serum bicarbonate and 24-hour survival.
- PMB administration before E. coli LPS challenge significantly increased serum bicarbonate, decreased TNF levels, and improved 24-hour survival.
- In vitro studies confirmed PMB neutralized E. coli LPS but not meningococcal LOS.
Conclusions:
- Polymyxin B pretreatment does not protect against shock induced by meningococcal LOS in rabbits.
- PMB demonstrates protective effects against E. coli LPS-induced shock, indicating differential activity against bacterial endotoxins.
- The findings suggest that PMB's efficacy in septic shock may depend on the specific bacterial pathogen and its endotoxin structure.