title: Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of tazobactam/piperacillin in a neutropenic mouse model of polymicrobial peritonitis.
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 C1), 1mg/kg of tachyplesin III, 120 mg/kg of TZP, 0.1mg/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.
authors: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy. anconacmi@interfree.it <anconacmi@interfree.it>
authors: Oscar
authors: O
authors: Cirioni
authors: Roberto
authors: R
authors: Ghiselli
authors: Wojciech
authors: W
authors: Kamysz
authors: Fiorenza
authors: F
authors: Orlando
authors: Carmela
authors: C
authors: Silvestri
authors: Federico
authors: F
authors: Mocchegiani
authors: Fabio
authors: F
authors: Di Matteo
authors: Elzbieta
authors: E
authors: Kamysz
authors: Alessandra
authors: A
authors: Riva
authors: Marco
authors: M
authors: Rocchi
authors: Vittorio
authors: V
authors: Saba
authors: Giorgio
authors: G
authors: Scalise
authors: Andrea
authors: A
authors: Giacometti
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D010878:Piperacillin / Q000627:therapeutic use*; D015996:Survival Rate; D000078142:Tazobactam; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D010456:Peptides, Cyclic; C057636:tachyplesin peptide, Tachypleus tridentatus; D016179:Granulocyte Colony-Stimulating Factor; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin