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), 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-alpha 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.
Ghiselli
Roberto
R
Department of General Surgery I, INRCA IRRCS, University of Ancona, Ancona, Italy.
Giacometti
Andrea
A
Cirioni
Oscar
O
Mocchegiani
Federico
F
Viticchi
Claudio
C
Scalise
Giorgio
G
Saba
Vittorio
V
D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004731:Endotoxins / Q000097:blood; D005122:Exudates and Transudates / Q000382:microbiology; D015378:Imipenem / Q000494:pharmacology*; D008297:Male; D010538:Peritonitis / Q000188:drug therapy* / Q000401:mortality; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004731:Endotoxins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C097849:buforin II; D015378:Imipenem; D019980:Amoxicillin-Potassium Clavulanate Combination; D003091:Colistin