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Endotoxin filtration and immune stimulation improve survival from gram-negative sepsis
W G Cheadle1, K Hanasawa, R N Gallinaro
1Department of Surgery, University of Louisville, KY 40292.
Abstract:
Polymyxin B, when bound to a polystyrene fiber (PMX-F), has been used experimentally as an extracorporeal blood filter to reduce serum lipopolysaccharide levels, which are believed to be responsible for physiologic alterations in the septic state. To validate our theory that a combination of PMX-F, systemic antibiotics, and immune stimulation would improve survival, 78 rats were given intravenous doses of Escherichia coli (range, 4.6 to 6.2 X 10(8) colony-forming units/ml). They were then randomized into groups receiving either systemic gentamicin (n = 10); pretreatment with muramyl dipeptide (n = 11); or extracorporeal hemoperfusion through either a sham column (n = 8), PMX-F-packed column with systemic gentamicin (n = 8); or PMX-F-packed column with systemic gentamicin and muramyl dipeptide pretreatment (n = 8). Thirty-three control rats received no treatment. Sham hemoperfusion (13%) and control (21%) rats had the lowest survival rate, although increased improvement was noted in rats treated with gentamicin (30%) or the combination of PMX-F filtration and gentamicin (50%). The most significant improvements occurred in rats pretreated with muramyl dipeptide (53%) and in rats treated with a combination of PMX-F, gentamicin, and muramyl dipeptide (88%). These data show that lipopolysaccharide filtration and nonspecific immune stimulation are additive to antibiotic therapy and are useful as adjunctive measures in the multimodal treatment of experimental gram-negative bacterial infection.
Insights
Combining Polymyxin B fiber (PMX-F) filtration, antibiotics, and immune stimulation significantly improved survival in experimental gram-negative infections. This multimodal approach offers a promising adjunctive therapy for sepsis.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Biomedical Engineering
Background:
- Sepsis involves physiologic alterations linked to elevated serum lipopolysaccharide (LPS).
- Extracorporeal blood filtration using Polymyxin B immobilized on a polystyrene fiber (PMX-F) can reduce LPS levels.
- Adjunctive therapies to antibiotics are crucial for improving outcomes in severe infections.
Purpose of the Study:
- To validate the hypothesis that a combination of PMX-F hemoperfusion, systemic antibiotics, and immune stimulation enhances survival in experimental gram-negative bacterial infection.
- To assess the additive effects of LPS filtration and immune modulation alongside antibiotic treatment.
Main Methods:
- Seventy-eight rats were intravenously administered Escherichia coli.
- Rats were randomized into groups receiving systemic gentamicin, muramyl dipeptide pretreatment, sham hemoperfusion, PMX-F hemoperfusion with gentamicin, or PMX-F hemoperfusion with gentamicin and muramyl dipeptide.
- Survival rates were compared across treatment and control groups.
Main Results:
- Control and sham hemoperfusion groups exhibited the lowest survival rates (21% and 13%, respectively).
- Gentamicin treatment improved survival to 30%, and PMX-F filtration with gentamicin increased it to 50%.
- Muramyl dipeptide pretreatment yielded 53% survival, while the combination of PMX-F, gentamicin, and muramyl dipeptide achieved 88% survival.
Conclusions:
- Lipopolysaccharide filtration and nonspecific immune stimulation demonstrate additive benefits to antibiotic therapy.
- This multimodal strategy, combining PMX-F, antibiotics, and immune stimulation, is effective as an adjunctive treatment for experimental gram-negative bacterial infections.
- The findings support the use of LPS adsorption and immune modulation in managing sepsis.