Single-dose intraperitoneal magainins improve survival in a gram-negative-pathogen septic shock rat model.
The therapeutic efficacies of three polycationic peptides selected among the class of the magainins (magainin I, magainin II, and magainin II amide), alone and combined with piperacillin, were investigated in a rat model of septic shock. Rats were given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli and randomized to receive intraperitoneally isotonic sodium chloride solution, 60 mg of piperacillin per kg of body weight, and 1 mg of each magainin per kg alone and combined with 60 mg of piperacillin per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatments with the magainins achieved significant reductions of bacterial growth and plasma endotoxin and TNF-alpha concentrations. In general, treatments with the combinations of magainins and piperacillin demonstrated the highest efficacies.
Cirioni
Oscar
O
Institute of Infectious Diseases and Public Health, University of Ancona, Italy. anconacmi@interfree.it
Giacometti
Andrea
A
Ghiselli
Roberto
R
Mocchegiani
Federico
F
Fineo
Anna
A
Orlando
Fiorenza
F
Del Prete
Maria Simona
MS
Rocchi
Marco
M
Saba
Vittorio
V
Scalise
Giorgio
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D007263:Infusions, Parenteral; D054806:Magainins; D008297:Male; D008826:Microbial Sensitivity Tests; D010878:Piperacillin / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy*; D016896:Treatment Outcome; D029867:Xenopus Proteins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054806:Magainins; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C053300:magainin 1 peptide, Xenopus; D010878:Piperacillin