Efficacy of cefepime, ertapenem and norfloxacin against leptospirosis and for the clearance of pathogens in a hamster model

Efficacy of cefepime, ertapenem and norfloxacin against leptospirosis and for the clearance of pathogens in a hamster model
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头孢吡肟、厄他培南和诺氟沙星在仓鼠模型中对抗钩端螺旋体病和清除病原体的功效

DOI:
10.1016/j.micpath.2014.11.006
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发表时间:
2014-12-01
影响因子:
3.8
通讯作者:
Cao, Yongguo
Cao, Yongguo
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Wenlong;Zhang, Naisheng;Cao, Yongguo

文献摘要

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患有严重钩端螺旋体病的动物和人可能需要经验性治疗。虽然许多抗生素在体外对多种钩端螺旋体血清型有效,但其体内疗效有限。我们评估了头孢吡肟(日剂量:2、5、10和20 mg/kg)、厄他培南(日剂量:2.5、5和10 mg/kg)和诺氟沙星(日剂量:20、40和80 mg/kg)治疗钩端螺旋体病的疗效,以及在使用秋血清型钩端螺旋体的致死性仓鼠模型中清除靶器官(肝、肾、肺、心和脾)钩端螺旋体的能力。采用苏木精和伊红染色(H&E染色)观察感染肾、肺和肝的组织病理学变化。所有未经治疗的动物作为阴性对照,在感染后第5天至第7天因靶器官中存在钩端螺旋体而死亡。与未治疗组相比,所有治疗组的生存率均有所提高,并且靶器官中钩端螺旋体的存在呈剂量依赖性减少。头孢吡肟的生存效益与标准治疗强力霉素相当。我们得出的结论是,所有在体内测试的抗生素都能产生统计学上显著的生存优势,减轻组织损伤,减少靶器官中钩端螺旋体的丰度。(C) 2014 Elsevier Ltd.版权所有。
Animals and humans with severe leptospirosis may require empirical treatment. Although many antibiotics are active against multiple leptospira serovars in vitro, their efficacy in vivo is limited. We evaluated the efficacy of cefepime (daily dose: 2, 5, 10, and 20 mg/kg), ertapenem (daily dose: 2.5, 5, and 10 mg/kg) and norfloxacin (daily dose: 20, 40, and 80 mg/kg) for the treatment of leptospirosis and the ability to clear leptospira in target organs (liver, kidney, lung, heart, and spleen) in a lethal hamster model using Leptospira interrogans serovar Autumnalis. The histopathology of infected kidney, lung and liver was also evaluated using hematoxylin and eosin stain (H&E stain). All untreated animals, serving as a negative control, died with leptospira existing in the target organs between the 5th and 7th day after infection. All of the treated groups displayed improved survival compared to the untreated group and demonstrated a dose-dependent decrease in the presence of leptospira in the target organs. Cefepime showed survival benefit comparable to the standard treatment, doxycycline. We conclude that all of the antibiotics tested in vivo produce a statistically significant survival advantage, alleviate tissue injury and decrease the abundance of leptospira in target organs. (C) 2014 Elsevier Ltd. All rights reserved.