Pretreatment with the protegrin IB-367 affects gram-positive biofilm and enhances the therapeutic efficacy of linezolid in animal models of central venous catheter infection

Roberto Ghiselli, Andrea Giacometti, Oscar Cirioni, Federico Mocchegiani, Carmela Silvestri, Fiorenza Orlando, Wojciech Kamysz, Alberto Licci, Piotr Nadolski, Agnese Della Vittoria, Jerzy Łukasiak, Giorgio Scalise, Vittorio Saba

Research output: Contribution to journalArticle

Abstract

Background: Biofilms play an important role in the pathogenesis of several chronic infections and nosocomial infections related to indwelling medical devices. Methods: To assess the efficacy of IB-367 and linezolid (LZD) in the treatment of central venous catheter (CVC) infections using the antibiotic-lock technique, in vitro and in vivo studies were performed. The in vitro antibiotic susceptibility assay for Staphylococcus aureus and Enterococcus faecalis biofilms developed on 96-well polystyrene tissue culture plates was performed to determine the activity of the compounds. Efficacy studies were performed in rat models of Gram-positive CVC infection. Silastic catheters were implanted into the superior cava of adult male Wistar rats. Twenty-four hours after implantation, the catheters were pretreated by filling with IB-367. Thirty minutes later, rats were challenged via the CVC with 1.0 × 106 CFU (colony forming units) of S aureus strain diffuse Smith and clinical isolate of slime-producing E faecalis. Administration of LZD into the CVC at a concentration equal to the minimum bacteriocidal concentration observed using adherent cells or at a much higher concentration (1024 μg/mL) began 24 hours later. Results: Both for S aureus and E faecalis, the killing activities of LZD against adherent bacteria were at least 4-fold to 8-fold lower than that against freely growing cells. For both strains, in IB-367-pretreated wells, LZD strongly increases its activity. The in vivo studies showed that when CVCs were pretreated with IB-367, Gram-positive biofilm bacterial load was further decreased to 101 CFU/mL and bacteremia was not detected. Conclusions: IB-367 has potential as an adjunctive agent to LZD in the treatment of Gram-positive biofilm infections such as CVC infections.

Original languageEnglish
Pages (from-to)463-468
Number of pages6
JournalJournal of Parenteral and Enteral Nutrition
Volume31
Issue number6
DOIs
Publication statusPublished - Nov 2007

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)

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    Ghiselli, R., Giacometti, A., Cirioni, O., Mocchegiani, F., Silvestri, C., Orlando, F., Kamysz, W., Licci, A., Nadolski, P., Della Vittoria, A., Łukasiak, J., Scalise, G., & Saba, V. (2007). Pretreatment with the protegrin IB-367 affects gram-positive biofilm and enhances the therapeutic efficacy of linezolid in animal models of central venous catheter infection. Journal of Parenteral and Enteral Nutrition, 31(6), 463-468. https://doi.org/10.1177/0148607107031006463