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.
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: Ana Motos; Gianluigi Li Bassi; Francesco Pagliara; Laia Fernandez-Barat; Hua Yang; Eli Aguilera Xiol; Tarek Senussi; Francesco A Idone; Chiara Travierso; Chiara Chiurazzi; Rosanel Amaro; Minlan Yang; Joaquim Bobi; Montserrat Rigol; David P Nicolau; Gerard Frigola; Roberto Cabrera; Jose Ramirez; Paolo Pelosi; Francesco Blasi; Massimo Antonelli; Antonio Artigas; Jordi Vila; Marin Kollef; Antoni Torres Journal: Antimicrob Agents Chemother Date: 2021-01-20 Impact factor: 5.191
Authors: Steven Y C Tong; Joshua S Davis; Emily Eichenberger; Thomas L Holland; Vance G Fowler Journal: Clin Microbiol Rev Date: 2015-07 Impact factor: 26.132
Authors: Alexander J Lepak; Karen Marchillo; Solen Pichereau; William A Craig; David R Andes Journal: Antimicrob Agents Chemother Date: 2012-09-10 Impact factor: 5.191
Authors: D Battaglini; A Motos; G Li Bassi; H Yang; F Pagliara; M Yang; E Aguilera Xiol; A Meli; J Bobi; G Frigola; T Senussi; F Idone; C Travierso; C Chiurazzi; L Fernandez-Barat; M Rigol; J Ramirez; P Pelosi; D Chiumello; M Antonelli; D P Nicolau; J Bringue; A Artigas; L Guerrero; D Soy; A Torres Journal: Antimicrob Agents Chemother Date: 2020-12-16 Impact factor: 5.191