title: Efficacy of the combination of tachyplesin III and clarithromycin in rat models of Escherichia coli sepsis.
abstract: 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.
authors.affiliation: Clinica Malattie Infettive, c/o Ospedale Regionale, Via Conca 71, 60020 Torrette AN, Italy. anconacmi@interfree.it
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Alessandra
authors.initials: A
authors.lastname: Riva
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kamysz
authors.forename: Sefora
authors.initials: S
authors.lastname: Castelletti
authors.forename: Marco
authors.initials: M
authors.lastname: Rocchi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Saba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
mesh_terms: 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
chemical_list: 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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