Antiendotoxin activity of protegrin analog IB-367 alone or in combination with piperacillin in different animal models of septic shock.
The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E. coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin. The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent. Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach.
Giacometti
Andrea
A
Institute of Infectious Diseases and Public Health, Clinica delle Malattie Infettive, Università Politecnica delle Marche, c/o Ospedale Regionale, Via Conca, 60020 Torrette AN, Ancona, Italy. anconacmi@interfree.it
Cirioni
Oscar
O
Ghiselli
Roberto
R
Mocchegiani
Federico
F
Viticchi
Claudio
C
Orlando
Fiorenza
F
D'Amato
Giuseppina
G
Del Prete
Maria Simona
MS
Kamysz
Wojciech
W
łLukasiak
Jerzy
J
Saba
Vittorio
V
Scalise
Giorgio
G
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D002432:Cecum / Q000601:surgery; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy*; D008026:Ligation; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010538:Peritonitis / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D010878:Piperacillin / Q000008:administration & dosage* / Q000627:therapeutic use*; D011506:Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology
D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D010455:Peptides; D011506:Proteins; C119872:antimicrobial peptide IB-367; D010878:Piperacillin