Efficacy of the combination of tachyplesin III and clarithromycin in rat models of Escherichia coli sepsis.
We investigated the efficacy of tachyplesin III and clarithromycin in two experimental rat models of severe gram-negative bacterial infections. Adult male Wistar rats were given either (i) an intraperitoneal injection of 1 mg/kg Escherichia coli 0111:B4 lipopolysaccharide or (ii) 2 x 10(10) CFU of E. coli ATCC 25922. For each model, the animals received isotonic sodium chloride solution, 1 mg/kg tachyplesin III, 50 mg/kg clarithromycin, or 1 mg/kg tachyplesin III combined with 50 mg/kg clarithromycin intraperitoneally. Lethality, bacterial growth in the blood and peritoneum, and the concentrations of endotoxin and tumor necrosis factor alpha (TNF-alpha) in plasma were evaluated. All the compounds reduced the lethality of the infections compared to that for the controls. Tachyplesin III exerted a strong antimicrobial activity and achieved a significant reduction of endotoxin and TNF-alpha concentrations in plasma compared to those of the control and clarithromycin-treated groups. Clarithromycin exhibited no antimicrobial activity but had a good impact on endotoxin and TNF-alpha plasma concentrations. A combination of tachyplesin III and clarithromycin resulted in significant reductions in bacterial counts and proved to be the most-effective treatment in reducing all variables measured.
Cirioni
Oscar
O
Clinica Malattie Infettive, c/o Ospedale Regionale, Via Conca 71, 60020 Torrette AN, Italy. anconacmi@interfree.it
Ghiselli
Roberto
R
Silvestri
Carmela
C
Kamysz
Wojciech
W
Orlando
Fiorenza
F
Riva
Alessandra
A
Kamysz
Elzbieta
E
Castelletti
Sefora
S
Rocchi
Marco
M
Saba
Vittorio
V
Scalise
Giorgio
G
Giacometti
Andrea
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000627:therapeutic use; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D004731:Endotoxins; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C057636:tachyplesin peptide, Tachypleus tridentatus; D017291:Clarithromycin
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