Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia

特拉万星与利奈唑胺在猪重症耐甲氧西林金黄色葡萄球菌肺炎模型中的疗效比较

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作者: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

Abstract

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 106 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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