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Carbapenem-induced endotoxin release in gram-negative bacterial sepsis rat models
T Horii1, M Kobayashi, M Nadai
1Department of Bacteriology, Nagoya University School of Medicine, Japan. horii@tsuru.med.nagoya-u.ac.jp
Abstract:
The carbapenem-induced endotoxin release was evaluated using experimental models of gram-negative bacterial sepsis in Wistar rats. Infections with Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris and Proteus mirabilis resulted in an increase of the plasma endotoxin concentration after treatment with ceftazidime and carbapenems including imipenem, panipenem, meropenem and biapenem. Except for P. aeruginosa, the plasma endotoxin concentrations after carbapenem treatment were significantly lower than those after ceftazidime treatment. It is noteworthy that treatment of P. aeruginosa sepsis with meropenem or biapenem induced significantly more endotoxin release than other carbapenems and the endotoxin concentrations induced by these carbapenems reached those of ceftazidime treatment. The plasma endotoxin concentrations appeared to correlate with the reduction of platelet counts and the elevation of both glutamic oxaloacetic transaminase and glutamic pyruvic transaminase values.
Insights
Carbapenem antibiotics generally reduced endotoxin release in gram-negative bacterial sepsis models compared to ceftazidime. However, meropenem and biapenem showed increased endotoxin release in Pseudomonas aeruginosa sepsis.
Area of Science:
- Microbiology
- Pharmacology
- Toxicology
Background:
- Gram-negative bacterial sepsis is a critical condition.
- Endotoxin release during treatment can exacerbate sepsis severity.
- Carbapenems are broad-spectrum antibiotics used for severe infections.
Purpose of the Study:
- To compare endotoxin release induced by carbapenems versus ceftazidime in experimental gram-negative bacterial sepsis.
- To investigate the impact of specific carbapenems on endotoxin release in Pseudomonas aeruginosa sepsis.
Main Methods:
- Experimental sepsis models in Wistar rats infected with various Gram-negative bacteria (E. coli, S. marcescens, K. pneumoniae, P. aeruginosa, P. vulgaris, P. mirabilis).
- Treatment with ceftazidime and carbapenems (imipenem, panipenem, meropenem, biapenem).
- Measurement of plasma endotoxin concentrations, platelet counts, and liver enzymes (AST, ALT).
Main Results:
- Carbapenems, except in P. aeruginosa infections, induced significantly lower plasma endotoxin concentrations than ceftazidime.
- Meropenem and biapenem treatments for P. aeruginosa sepsis resulted in higher endotoxin release compared to other carbapenems, comparable to ceftazidime levels.
- Elevated plasma endotoxin correlated with decreased platelet counts and increased AST/ALT levels.
Conclusions:
- Carbapenems are generally associated with less endotoxin release than ceftazidime in Gram-negative sepsis.
- Specific carbapenems (meropenem, biapenem) may induce more endotoxin release in P. aeruginosa sepsis.
- Endotoxin levels correlate with markers of sepsis severity and organ damage.