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替拉万星治疗猪耐甲氧西林金黄色葡萄球菌性重症肺炎的疗效与利奈唑胺比较。

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

机构信息

Division of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain.

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.

出版信息

Antimicrob Agents Chemother. 2020 Dec 16;65(1). doi: 10.1128/AAC.01009-20.

Abstract

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant (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 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 ( = 0.019), with the lowest MRSA lung burden in the telavancin group ( < 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 ( < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid ( = 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.

摘要

目前的指南建议万古霉素和利奈唑胺作为治疗耐甲氧西林金黄色葡萄球菌(MRSA)医院获得性肺炎的一线药物。替拉万星是一种潜在的新治疗选择,特别是在单一微生物 MRSA 肺炎中。本研究比较了替拉万星与利奈唑胺在严重 MRSA 肺炎猪模型中的疗效。在 18 头机械通气的猪(32.11±1.18kg)中,每个肺叶给予 75ml 10 CFU/ml 的 MRSA。肺炎发作后,猪被随机分为三组:对照组、每 24 小时接受 22.5mg/kg 替拉万星的治疗组和每 12 小时接受 10mg/kg 利奈唑胺静脉注射的治疗组。每 24 小时采集气管吸出物和支气管肺泡灌洗液(BAL)进行培养。治疗 48 小时后,从每个肺叶的腹侧和背侧采集组织样本。进行微生物学和组织病理学分析。各组肺组织浓度不同( = 0.019),替拉万星组的 MRSA 肺部负担最低( < 0.05 与对照组相比)。在对照组、利奈唑胺组和替拉万星组的肺组织样本中,分别有 46.7%、40.0%和 21.7%检测到 MRSA( < 0.001)。气管吸出物中的 MRSA 浓度在各组之间存在差异( = 0.011),但在 BAL 液中没有差异。此外,在使用替拉万星期间没有增加肾损伤的风险。因此,在严重 MRSA 肺炎猪模型中,替拉万星在治疗的前 48 小时内比利奈唑胺具有更高的杀菌效果。然而,需要进一步的研究来证实替拉万星治疗 MRSA 医院获得性肺炎的益处。

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