Cationic Peptides Combined with Betalactams Reduce Mortality from Peritonitis in Experimental Rat Model

The efficacy of cationic peptides combined with betalactams was investigated in a peritonitis rat model. Intraabdominal sepsis was induced in adult Wistar rats via cecal ligation and single puncture. The study included eight drug-treated groups: each of them received intravenous polymyxin-E (1 mg/kg...

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Bibliographic Details
Published in:The Journal of surgical research 2002-11, Vol.108 (1), p.107-111
Main Authors: Ghiselli, Roberto, Giacometti, Andrea, Cirioni, Oscar, Mocchegiani, Federico, Viticchi, Claudio, Scalise, Giorgio, Saba, Vittorio
Format: Article
Language:English
Subjects:
Abdomen
Amoxicillin-Potassium Clavulanate Combination - pharmacology
Animals
Anti-Bacterial Agents - pharmacology
Antimicrobial Cationic Peptides - pharmacology
Biological and medical sciences
Colistin - pharmacology
Colony Count, Microbial
Disease Models, Animal
Drug Therapy, Combination
Endotoxins - blood
Exudates and Transudates - microbiology
Gastroenterology. Liver. Pancreas. Abdomen
Imipenem - pharmacology
Male
Medical sciences
Other diseases. Semiology
Peritonitis - drug therapy
Peritonitis - mortality
Proteins - pharmacology
Rats
Rats, Wistar
Sepsis - drug therapy
Sepsis - mortality
Tumor Necrosis Factor-alpha - metabolism
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Summary:The efficacy of cationic peptides combined with betalactams was investigated in a peritonitis rat model. Intraabdominal sepsis was induced in adult Wistar rats via cecal ligation and single puncture. The study included eight drug-treated groups: each of them received intravenous polymyxin-E (1 mg/kg), buforin II (1 mg/kg), imipenem (20 mg/kg), amoxicillin-clavulanate (50 mg/kg), polymyxin-E (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg), and buforin II (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg). The study included an untreated control group that received intravenous isotonic sodium chloride solution. All compounds significantly reduced the lethality and the number of bacteria in abdominal fluid compared with saline treatment. Among compounds, imipenem showed the highest antimicrobial activity, while buforin II produced the highest reduction in plasma endotoxin and TNF-α levels. Overall, buforin II and imipenem association were the most effective therapeutic approach. Data presented here suggest the potential advantages of combining antimicrobial agents and compounds able to neutralize the biological effect of the endotoxin.
ISSN:0022-4804
1095-8673
DOI:10.1006/jsre.2002.6518