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Polymyxin B moderates acidosis and hypotension in established, experimental gram-negative septicemia
P M Flynn1, J L Shenep, D C Stokes
1Division of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Abstract:
Polymyxin B (PMB), an antibiotic, and sodium deoxycholate (NaD), a bile salt, are surface-active agents. Each protected mice against an otherwise lethal challenge with purified endotoxin (P less than .001). To determine if either of these agents was effective in treating established, overwhelming gram-negative septicemia, we infected rabbits by intraperitoneal injection of Escherichia coli K1. Animals were treated with moxalactam 1 hr after infection, then randomly assigned to groups receiving either saline, PMB, or NaD. Serial samples of blood were assayed for bacterial concentration, levels of plasma endotoxin, arterial blood gases, and complete blood cell counts. Physiologic functions were monitored continuously. Although levels of bacteremia and endotoxemia were similar in all three groups, rabbits receiving PMB had significantly higher mean arterial blood pressure, blood pH, and bicarbonate concentrations than did control rabbits (P less than .05). Rabbits receiving NaD fared no better than controls. In this model, PMB moderates some of the deleterious effects of established, overwhelming gram-negative bacterial sepsis.
Insights
Polymyxin B (PMB) showed promise in treating severe gram-negative bacterial sepsis in rabbits. While not reducing bacterial or endotoxin levels, PMB improved key physiological markers, unlike sodium deoxycholate (NaD).
Area of Science:
- Microbiology
- Pharmacology
- Critical Care Medicine
Background:
- Gram-negative bacterial sepsis is a life-threatening condition often associated with high endotoxin levels.
- Polymyxin B (PMB) and sodium deoxycholate (NaD) are surface-active agents with known endotoxin-neutralizing properties.
- The efficacy of these agents in treating established sepsis, beyond initial endotoxin challenge, requires further investigation.
Purpose of the Study:
- To evaluate the therapeutic potential of Polymyxin B (PMB) and sodium deoxycholate (NaD) in a rabbit model of established, overwhelming gram-negative bacterial sepsis.
- To assess the impact of PMB and NaD on key physiological parameters and markers of sepsis severity.
Main Methods:
- Rabbits were infected with Escherichia coli K1 and treated with moxalactam.
- Following initial treatment, animals were randomly assigned to receive saline, PMB, or NaD.
- Serial blood samples were analyzed for bacterial and endotoxin concentrations, arterial blood gases, and complete blood cell counts.
- Continuous monitoring of physiological functions was performed.
Main Results:
- Levels of bacteremia and endotoxemia were comparable across all treatment groups (saline, PMB, NaD).
- Rabbits treated with PMB demonstrated significantly improved mean arterial blood pressure, blood pH, and bicarbonate concentrations compared to controls (P < .05).
- Sodium deoxycholate (NaD) treatment did not yield significant improvements over the control group.
Conclusions:
- Polymyxin B (PMB) may moderate some detrimental physiological effects of established, overwhelming gram-negative bacterial sepsis.
- Sodium deoxycholate (NaD) was not found to be effective in this model of established sepsis.
- These findings suggest a potential role for PMB in supportive care for severe gram-negative sepsis, independent of direct bacterial or endotoxin load reduction.