• Mariano Esperatti, Gianluigi Li Bassi, Dolors Soy, Laura Guerrero, Montserrat Rigol, Pilar Martinez-Olondris, Carlos Agusti, Maria Angels Quera, Manto Liapikou, Xavier Filella, and Jordi Puig de la Bellacasa.
• Pneumology Service, Thorax Clinic Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques Agustí Pi Sunyer, University of Barcelona, Barcelona, Spain.
• Crit. Care Med.. 2012 Jan 1;40(1):162-8.

ObjectiveTo assess the efficacy of linezolid compared with vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) in ventilated pigs.MethodsForty 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.ResultsA 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.ConclusionsIn this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.

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