title: Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs.
abstract: OBJECTIVE
  To assess the efficacy of linezolid compared with vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) in ventilated pigs.
  
  
  METHODS
  Forty pigs (30 kg) were intubated and challenged via bronchoscopy with a suspension of 106 colony forming units of MRSA into every lobe. Afterwards, pigs were ventilated up to 96 hours. Twelve hours after bacterial inoculation, the animals were randomized into 4 groups of treatment: group 1, control; group 2, vancomycin twice daily; group 3, continuous infusion of vancomycin; and group 4, linezolid. Clinical and laboratory parameters were monitored throughout the study. Bacterial cultures of bronchoalveolar lavage fluid and lung tissue samples were performed at the end of the study. Measurements of histopathology derangements of lung samples and studies of intrapulmonary drug penetration were performed.
  
  
  RESULTS
  A total of 34 animals completed the study. No differences in clinical and laboratory parameters were observed. The percentage of bronchoalveolar lavage fluid and lung tissue samples with positive cultures for MRSA in controls and groups 2, 3, and 4 was respectively 75%, 11%, 11%, and 0% (p < .01); 52%, 9%, 24%, and 2.5% (p < .01). Histopathology studies demonstrated signs of pneumonia in 95%, 69%, 58%, and 57% and signs of severe pneumonia in 48%, 29%, 22%, and 0% of controls and groups 2, 3, and 4, respectively (p < .01). In addition, pharmacokinetics/pharmacodynamics profile in serum and lung tissue showed better results for linezolid compared with both vancomycin treatments.
  
  
  CONCLUSIONS
  In this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.
authors.affiliation: Pneumology Service, Thorax Clinic Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques Agustí Pi Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez-Olondris
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rigol
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.forename: Laura
authors.initials: L
authors.lastname: Guerrero
authors.forename: Carlos
authors.initials: C
authors.lastname: Agusti
authors.forename: Maria Angels
authors.initials: MA
authors.lastname: Quera
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Li Bassi
authors.forename: Mariano
authors.initials: M
authors.lastname: Esperatti
authors.forename: Nestor
authors.initials: N
authors.lastname: Luque
authors.forename: Manto
authors.initials: M
authors.lastname: Liapikou
authors.forename: Xavier
authors.initials: X
authors.lastname: Filella
authors.forename: Francesc
authors.initials: F
authors.lastname: Marco
authors.forename: Jordi Puig
authors.initials: JP
authors.lastname: de la Bellacasa
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*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood; D000069349:Linezolid; D008168:Lung / Q000473:pathology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D023303:Oxazolidinones / Q000627:therapeutic use*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D012121:Respiration, Artificial / Q000009:adverse effects; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D016209:Interleukin-8; D023303:Oxazolidinones; D014409:Tumor Necrosis Factor-alpha; D014640:Vancomycin; D000069349:Linezolid