Efficacy of the combination of tachyplesin III and clarithromycin in rat models of Escherichia coli sepsis

Oscar Cirioni, Roberto Ghiselli, Carmela Silvestri, Wojciech Kamysz, Fiorenza Orlando, Alessandra Riva, Elzbieta Kamysz, Sefora Castelletti, Marco Rocchi, Vittorio Saba, Giorgio Scalise, Andrea Giacometti

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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 × 1010 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-α) 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-α 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-α 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.

Original languageEnglish
Pages (from-to)4351-4355
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume52
Issue number12
DOIs
Publication statusPublished - Dec 2008

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ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Pharmacology

Cite this

Cirioni, O., Ghiselli, R., Silvestri, C., Kamysz, W., Orlando, F., Riva, A., Kamysz, E., Castelletti, S., Rocchi, M., Saba, V., Scalise, G., & Giacometti, A. (2008). Efficacy of the combination of tachyplesin III and clarithromycin in rat models of Escherichia coli sepsis. Antimicrobial Agents and Chemotherapy, 52(12), 4351-4355. https://doi.org/10.1128/AAC.00086-08