Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of tazobactam/piperacillin in a neutropenic mouse model of polymicrobial peritonitis

Oscar Cirioni, Roberto Ghiselli, Wojciech Kamysz, Fiorenza Orlando, Carmela Silvestri, Federico Mocchegiani, Fabio Di Matteo, Elzbieta Kamysz, Alessandra Riva, Marco Rocchi, Vittorio Saba, Giorgio Scalise, Andrea Giacometti

Research output: Contribution to journalArticle

Abstract

We investigated the efficacy of tazobactam/piperacillin (TZP), tachyplesin III and granulocyte-colony stimulating factor (G-CSF) in an experimental murine neutropenic intraabdominal infection. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 pre-infection. Septic shock was induced by cecal ligation and puncture. Animals received intravenously isotonic sodium chloride solution (control group C 1), 1 mg/kg of tachyplesin III, 120 mg/kg of TZP, 0.1 mg/kg of G-CSF, tachyplesin III plus TZP, G-CSF plus TZP and finally tachyplesin III plus G-CSF plus TZP, respectively. Lethality, bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes, endotoxin, IL-6 and TNF-alpha concentrations in plasma were evaluated. All compounds reduced the lethality when compared to controls. Endotoxin and cytokine plasma levels were significantly higher in TZP-treated animals compared to tachyplesin III-treated animals. Finally, all drug combinations showed to be the most effective treatment in reducing all variables measured. Interestingly, the strongest results concerning the bacterial growth inhibition, lethality and endotoxemia were obtained when the three compounds were contemporaneously administered. The presence of their positive interaction makes tachyplesin III and G-CSF potentially valuable as an adjuvant for antimicrobial chemotherapy of sepsis.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalPeptides
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • Antibiotics
  • Antimicrobial peptides
  • Endotoxin
  • Granulocyte-colony stimulating factor
  • Sepsis
  • Tachyplesin III
  • TNF-alpha

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Cirioni, O., Ghiselli, R., Kamysz, W., Orlando, F., Silvestri, C., Mocchegiani, F., Di Matteo, F., Kamysz, E., Riva, A., Rocchi, M., Saba, V., Scalise, G., & Giacometti, A. (2008). Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of tazobactam/piperacillin in a neutropenic mouse model of polymicrobial peritonitis. Peptides, 29(1), 31-38. https://doi.org/10.1016/j.peptides.2007.10.024