title: Linezolid limits burden of methicillin-resistant Staphylococcus aureus in biofilm of tracheal tubes.
abstract: OBJECTIVE
  To evaluate the effects of systemic treatment with linezolid compared with vancomycin on biofilm formation in mechanically ventilated pigs with severe methicillin-resistant Staphylococcus aureus-induced pneumonia.
  
  
  METHODS
  Prospective randomized animal study.
  
  
  METHODS
  Departments of Pneumology, Microbiology, and Pharmacy of the Hospital Clínic, Barcelona, and Scientific and Technological Services of the University of Barcelona.
  
  
  METHODS
  We prospectively analyzed 70 endotracheal tube samples. Endotracheal tubes were obtained from pigs either untreated (controls, n=20), or treated with vancomycin (n=32) or linezolid (n=18).
  
  
  METHODS
  The endotracheal tubes were obtained from a previous randomized study in tracheally intubated pigs with methicillin-resistant Staphylococcus aureus severe pneumonia, and mechanically ventilated for 69±16 hrs.
  
  
  RESULTS
  Distal and medial hemisections of the endotracheal tube were assessed to quantify methicillin-resistant Staphylococcus aureus burden, antibiotic biofilm concentration by high-performance liquid chromatography or bioassay, and biofilm thickness through scanning electron microscopy. We found a trend toward a significant variation in biofilm methicillin-resistant Staphylococcus aureus burden (log colony-forming unit/mL) among groups (p=.057), and the lowest bacterial burden was found in endotracheal tubes treated with linezolid (1.98±1.68) in comparison with untreated endotracheal tubes (3.72±2.20, p=.045) or those treated with vancomycin (2.97±2.43, p=.286). Biofilm linezolid concentration was 19-fold above the linezolid minimum inhibitory concentration, whereas biofilm vancomycin concentration (1.60±0.91 µg/mL) was consistently below or close to the vancomycin minimum inhibitory concentration. Biofilm was thicker in the vancomycin group (p=.077).
  
  
  CONCLUSIONS
  Systemic treatment with linezolid limits endotracheal tube biofilm development and methicillin-resistant Staphylococcus aureus burden. The potential clinical usefulness of linezolid in decreasing the risk of biofilm-related respiratory infections during prolonged tracheal intubation requires further investigation.
authors.affiliation: Ciberes (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, 06/06/0028), Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Fernández-Barat
authors.forename: Miquel
authors.initials: M
authors.lastname: Ferrer
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Sierra
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.forename: Laura
authors.initials: L
authors.lastname: Guerrero
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Li Bassi
authors.forename: Núria
authors.initials: N
authors.lastname: Cortadellas
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Olondris
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rigol
authors.forename: Mariano
authors.initials: M
authors.lastname: Esperatti
authors.forename: Néstor
authors.initials: N
authors.lastname: Luque
authors.forename: Lina María
authors.initials: LM
authors.lastname: Saucedo
authors.forename: Carlos
authors.initials: C
authors.lastname: Agustí
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects*; D007442:Intubation, Intratracheal / Q000009:adverse effects*; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D023303:Oxazolidinones / Q000627:therapeutic use*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D013552:Swine; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid