Cecropin B Enhances Betalactams Activities in Experimental Rat Models of Gram-Negative Septic Shock

Roberto Ghiselli, Andrea Giacometti, Oscar Cirioni, Federico Mocchegiani, Fiorenza Orlando, Giuseppina D'Amato, Valerio Sisti, Giorgio Scalise, Vittorio Saba

Research output: Contribution to journalArticle

Abstract

Objective: To investigate the efficacy of imipenem, piperacillin combined with cecropin B in the prevention of lethality in 2 rat models of septic shock. Main outcome measures were bacterial growth in blood and intra-abdominal fluid, endotoxin and TNF-α concentrations in plasma, and lethality. Background: Sepsis remains a serious clinical problem despite intense efforts to improve survival. It is a major cause of morbidity and mortality in hospitalized patients. The primary cause of Gram-negative shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of Gram-negative bacteria. Methods: Adult male Wistar rats were given (1) an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 LPS or (2) 2 × 1010 CFU of E. coli ATCC 25922. All animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg cecropin B, 20 mg/kg imipenem, and 120 mg/kg piperacillin alone and combined with 1 mg/kg cecropin B. Each group included 20 animals. Results: All compounds reduced the lethality when compared with controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. On the other hand, each betalactam determined an increase of plasma endotoxin and TNF-α concentration. Combination between cecropin B and betalactams showed to be the most effective treatment in reducing all variables measured. Conclusion: Cecropin B enhances betalactams activities in Gram-negative sepic shock rat models.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalAnnals of Surgery
Volume239
Issue number2
DOIs
Publication statusPublished - Feb 2004

ASJC Scopus subject areas

  • Surgery

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    Ghiselli, R., Giacometti, A., Cirioni, O., Mocchegiani, F., Orlando, F., D'Amato, G., Sisti, V., Scalise, G., & Saba, V. (2004). Cecropin B Enhances Betalactams Activities in Experimental Rat Models of Gram-Negative Septic Shock. Annals of Surgery, 239(2), 251-256. https://doi.org/10.1097/01.sla.0000108673.25385.03