title: 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.
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 x 10(6) 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 microg/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 10(1) 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.
authors.affiliation: Department of General Surgery, I.N.R.C.A. I.R.R.C.S., Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Federico
authors.initials: F
authors.lastname: Mocchegiani
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Alberto
authors.initials: A
authors.lastname: Licci
authors.forename: Piotr
authors.initials: P
authors.lastname: Nadolski
authors.forename: Agnese
authors.initials: A
authors.lastname: Della Vittoria
authors.forename: Jerzy
authors.initials: J
authors.lastname: Łukasiak
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
authors.forename: Vittorio
authors.initials: V
authors.lastname: Saba
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002405:Catheterization, Central Venous / Q000009:adverse effects; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects / Q000502:physiology; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control*; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D023303:Oxazolidinones; D010455:Peptides; D000069349:Linezolid; C119872:antimicrobial peptide IB-367