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新型碳青霉烯类药物对结核病有任何价值吗?

Are the Newer Carbapenems of Any Value against Tuberculosis.

作者信息

Gonzalo Ximena, Drobniewski Francis

机构信息

Department of Infectious Diseases, Faculty of Medicine, Imperial College, London W12 0NN, UK.

出版信息

Antibiotics (Basel). 2022 Aug 7;11(8):1070. doi: 10.3390/antibiotics11081070.

Abstract

Our aim was to assess whether newer carbapenems with a better administration profile than meropenem (ertapenem, faropenem and tebipenem) were more effective against including M/XDRTB and determine if there was a synergistic/antagonistic effect with amoxicillin or clavulanate (inhibitor of beta-lactamases that MTB possesses) in vitro. Whilst meropenem is given three times a day intravenously, ertapenem, though given parenterally, is given once a day, faropenem and tebipenem are given orally. Eighty-two clinical drug-sensitive and -resistant MTB strains and a laboratory strain, H37Rv, were assessed by a microdilution methodology against ertapenem, faropenem, tebipenem and meropenem with and without amoxicillin or clavulanic acid. Ertapenem showed a limited activity. The addition of amoxicillin and clavulanate did not translate into significant improvements in susceptibility. Sixty-two isolates (75.6%) exhibited susceptibility to faropenem; the addition of amoxicillin and clavulanate further reduced the MIC in some isolates. Faropenem showed a limited activity (MIC of 8 mg/L or lower) in 21 strains completely resistant to meropenem (MIC of 16 mg/L or higher). Fifteen of the meropenem-resistant strains were susceptible to tebipenem. Carbapenems' activity has been reported extensively. However, there remains uncertainty as to which of them is most active against TB and what the testing methodology should be.

摘要

我们的目的是评估与美罗培南相比具有更好给药特性的新型碳青霉烯类药物(厄他培南、法罗培南和替比培南)对包括多重/广泛耐药结核病(M/XDRTB)在内的结核菌是否更有效,并确定在体外与阿莫西林或克拉维酸(结核分枝杆菌所拥有的β-内酰胺酶抑制剂)联合使用时是否存在协同/拮抗作用。美罗培南需每日静脉注射三次,而厄他培南虽然也是胃肠外给药,但只需每日给药一次,法罗培南和替比培南则为口服给药。采用微量稀释法,对82株临床药物敏感和耐药的结核分枝杆菌菌株以及一株实验室菌株H37Rv,评估了它们对厄他培南、法罗培南、替比培南和美罗培南(分别添加或不添加阿莫西林或克拉维酸)的敏感性。厄他培南显示出有限的活性。添加阿莫西林和克拉维酸并未显著提高药敏性。62株分离株(75.6%)对法罗培南敏感;添加阿莫西林和克拉维酸在一些分离株中进一步降低了最低抑菌浓度(MIC)。法罗培南对21株对美罗培南完全耐药(MIC为16mg/L或更高)的菌株显示出有限的活性(MIC为8mg/L或更低)。15株对美罗培南耐药的菌株对替比培南敏感。碳青霉烯类药物的活性已有广泛报道。然而,对于它们中哪一种对结核病最具活性以及应采用何种检测方法仍存在不确定性。

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