tachyplesin-peptide--tachypleus-tridentatus and 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.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Clarithromycin; Disease Models, Animal; DNA-Binding Proteins; Drug Therapy, Combination; Endotoxins; Escherichia coli; Escherichia coli Infections; Humans; Male; Peptides, Cyclic; Rats; Rats, Wistar; Sepsis; Treatment Outcome; Tumor Necrosis Factor-alpha

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peptides, Cyclic; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Treatment Outcome