Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs
Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs
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DOI：
10.1097/ccm.0b013e31822d74a2
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发表时间：
2012-01-01
影响因子：
8.8
通讯作者：
Torres, Antoni
中科院分区：
文献类型：
--
作者：
Martinez-Olondris, Pilar;Rigol, Montserrat;Torres, Antoni
目的：为了评估利奈唑胺与万古霉素相比，在实验模型中的耐甲氧西林金黄色葡萄球菌（MRSA）在通气pigs.Methods：40只猪（30公斤）诱导的肺炎的疗效插管和挑战，通过支气管镜与106个菌落形成单位的MRSA悬浮液进入每个肺叶。之后，对猪进行通风长达96小时。细菌接种后12小时，将动物随机分为4个给药组：第1组，对照;第2组，万古霉素每日两次;第3组，万古霉素持续输注;第4组，利奈唑胺。在整个研究期间监测临床和实验室参数。研究结束时，对支气管肺泡灌洗液和肺组织样本进行细菌培养。肺组织病理学紊乱的测量和肺内药物渗透的研究performed.Results：共34只动物完成了这项研究。未观察到临床和实验室参数差异。对照组和第2、3、4组MRSA培养阳性的支气管肺泡灌洗液和肺组织样本百分比分别为75%、11%、11%和0%（p <0.01）; 52%、9%、24%和2.5%（p <0.01）。组织学研究表明，对照组和第2、3和4组分别有95%、69%、58%和57%的肺炎体征，48%、29%、22%和0%的严重肺炎体征（p <0.01）。此外，在血清和肺组织中的药代动力学/药效学曲线显示利奈唑胺与万古霉素treatment.Conclusions相比，结果更好：在MRSA肺炎的动物模型中，利奈唑胺显示出比万古霉素更好的疗效，因为更好的药代动力学/药效学指标。(Crit Care Med 2012; 40：162-168）
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. (Crit Care Med 2012; 40:162-168)