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碳青霉烯类联合克拉维酸对小鼠结核病的活性。

Activity of carbapenems combined with clavulanate against murine tuberculosis.

机构信息

Laboratoire de Bactériologie, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France.

出版信息

Antimicrob Agents Chemother. 2011 Jun;55(6):2597-600. doi: 10.1128/AAC.01824-10. Epub 2011 Mar 14.

Abstract

Although beta-lactam antibiotics are not considered as antituberculous drugs, it has been recently shown that the combination of carbapenems and clavulanate is bactericidal in vitro. We evaluated in a murine model of tuberculosis the activity of carbapenems alone and combined with clavulanate against Mycobacterium tuberculosis. Swiss mice infected intravenously with 3 x 10⁵ M. tuberculosis H37Rv were treated for 4 weeks with clavulanate alone or imipenem, meropenem, and ertapenem alone or combined with clavulanate, whereas a positive control group was treated with isoniazid, and a negative control group was held without treatment. The combination of imipenem or meropenem plus clavulanate significantly improved survival. Among groups of mice with 100% survival, only isoniazid reduced lung CFU counts; the carbapenem-clavulanate combinations did not prevent bacterial growth. Although less active than isoniazid, the combinations of imipenem or meropenem plus clavulanate improved the survival of mice infected with M. tuberculosis and should be further evaluated.

摘要

虽然β-内酰胺类抗生素不被认为是抗结核药物,但最近的研究表明,碳青霉烯类药物与克拉维酸联合使用在体外具有杀菌作用。我们在结核分枝杆菌感染的小鼠模型中评估了碳青霉烯类药物单独使用和与克拉维酸联合使用对结核分枝杆菌的活性。瑞士小鼠经静脉感染 3 x 10⁵ 株结核分枝杆菌 H37Rv,用克拉维酸单独或亚胺培南、美罗培南和厄他培南单独或联合克拉维酸治疗 4 周,阳性对照组用异烟肼治疗,阴性对照组不治疗。亚胺培南或美罗培南联合克拉维酸可显著提高生存率。在生存率为 100%的小鼠组中,只有异烟肼降低了肺 CFU 计数;碳青霉烯类-克拉维酸联合用药并不能阻止细菌生长。尽管不如异烟肼有效,但亚胺培南或美罗培南联合克拉维酸的联合用药改善了感染结核分枝杆菌的小鼠的生存率,值得进一步评估。

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