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Bacterial translocation in an experimental model of multiple organ dysfunctions
Konstantinos Louis1, Mihai G Netea, Dionyssia-Pinelopi Carrer
14th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
Background:
In order to investigate the hypothesis that bacterial translocation from the intestine contributes to death after multiple organ dysfunction syndrome (MODS), a sterile MODS model was studied.
Methods:
MODS was induced in 139 male C57BL/6 mice by lipopolysaccharide (LPS) (endotoxin) infusion followed by zymozan infusion in four groups: Α, sham-operation; Β, LPS; C, LPS + 0.8 g/kg zymozan; and D, LPS + 1.2 g/kg zymozan. Mice were sacrificed at 24 and 48 h for quantitative tissue cultures, isolation, and stimulation of splenocytes, measurement of apoptosis of lymphocytes and macrophages, and of serum LPS and survival. Some mice with MODS were treated with the antibiotic ertapenem.
Results:
Enterobacteriaceae and Enterococcus spp were isolated from tissues. Group D had the highest bacterial load and the shortest survival. Release of interleukin-10, of interleukin-17, and of intgerferon-γ by splenocytes and the rate of apoptosis did not concur with immune paralysis. Serum LPS concentrations were higher in mice with MODS versus controls. Ertapenem prolonged survival and decreased the bacterial load.
Conclusions:
Bacterial translocation seems to be an important contributor leading from MODS to death and suggests a change in therapy towards adaptation of antimicrobial treatment upon early signs of MODS.
Insights
Bacterial translocation from the gut contributes to death in multiple organ dysfunction syndrome (MODS). Early antimicrobial treatment, like ertapenem, improved survival by reducing bacterial load in this mouse model.
Area of Science:
- Microbiology
- Immunology
- Pathophysiology
Background:
- Investigating the role of bacterial translocation in multiple organ dysfunction syndrome (MODS) mortality.
- Utilizing a sterile MODS mouse model to test a specific hypothesis.
Purpose of the Study:
- To determine if bacterial translocation from the intestine contributes to death in MODS.
- To evaluate the efficacy of ertapenem in treating MODS.
Main Methods:
- Inducing MODS in mice via lipopolysaccharide (LPS) and zymozan infusions.
- Performing quantitative tissue cultures, splenocyte analysis, apoptosis, and serum LPS measurements.
- Administering the antibiotic ertapenem to some MODS mice.
Main Results:
- Enterobacteriaceae and Enterococcus spp. were isolated from tissues, with higher loads in the most severely affected group.
- Serum LPS levels were elevated in MODS mice; immune markers did not indicate paralysis.
- Ertapenem treatment significantly prolonged survival and reduced bacterial load.
Conclusions:
- Bacterial translocation is a key factor in MODS-related mortality.
- Antimicrobial therapy adapted to early MODS signs is suggested.
- The findings support a shift in therapeutic strategies for MODS.
