Efficacy Of Telavancin In Comparison To Linezolid In A Porcine Model Of Severe Methicillin-Resistant Staphylococcus Aureus Pneumonia

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

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY(2021)

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摘要
Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 +/- 1.18 kg), 75 ml of 10(6) CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.
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telavancin, linezolid, MRSA, severe pneumonia, pig, animal models, mechanical ventilation, porcine model
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