This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Ghiselli, R. Articles by Saba, V. Search for Related Content PubMed PubMed Citation Articles by Ghiselli, R. Articles by Saba, V. Social Bookmarking                         What's this?

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, MD, PhD^*, Andrea Giacometti, MD, Oscar Cirioni, MD, PhD, Federico Mocchegiani, MD, PhD^*, Carmela Silvestri, PhD, Fiorenza Orlando, PhD, Wojciech Kamysz, PhD, Alberto Licci, MD, PhD, Piotr Nadolski, PhD, Agnese Della Vittoria, MD, PhD, Jerzy ukasiak, PhD, Giorgio Scalise, MD^* and Vittorio Saba, MD

From the ^* Department of General Surgery, I.N.R.C.A. I.R.R.C.S., Università Politecnica delle Marche, Ancona, Italy; Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy; Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy; and the Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland

Correspondence: Andrea Giacometti, MD, Clinica delle Malattie Infettive, c/o Ospedale Regionale, Via Conca, 71, 60200 Ancona AN Italy. Electronic mail may be sent to anconacmi{at}interfree.it.

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 x 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.

Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 6, 463-468 (2007)
DOI: 10.1177/0148607107031006463


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Fernandez-Hidalgo, J. Gavalda, B. Almirante, M.-T. Martin, P. Lopez Onrubia, X. Gomis, and A. Pahissa Evaluation of linezolid, vancomycin, gentamicin and ciprofloxacin in a rabbit model of antibiotic-lock technique for Staphylococcus aureus catheter-related infection J. Antimicrob. Chemother., March 1, 2010; 65(3): 525 - 530. [Abstract] [Full Text] [PDF]