Development of a penem antibiotic against Mycobacteroides abscessus.
Development of a penem antibiotic against Mycobacteroides abscessus.
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DOI：
10.1038/s42003-020-01475-2
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发表时间：
2020-12-07
影响因子：
5.9
通讯作者：
Townsend CA
中科院分区：
文献类型：
--
作者：
Batchelder HR;Story-Roller E;Lloyd EP;Kaushik A;Bigelow KM;Maggioncalda EC;Nuermberger EL;Lamichhane G;Townsend CA
β-内酰胺类是治疗人类细菌感染最广泛使用的抗生素类别。结核分枝杆菌是一种新兴的肺部病原体，对大多数抗生素（包括青霉素和头孢菌素）具有耐药性。由于目前没有FDA批准的治疗和治愈率<50%，因此迫切需要有效的治疗方法。本文报道了一种新的青霉烯类β-内酰胺类抗生素T405。从囊性纤维化患者中分离出的一组耐药菌株。此外，与β-内酰胺酶抑制剂阿维巴坦联合使用时，M.对T405的抑制作用接近检测极限。最后，我们显示了T405在小鼠中的有利药代动力学特征，并且在升高的剂量下没有毒性，这支持了该化合物的临床潜力。Batchelder等报道了一种新的青霉烯类抗生素T405，它对M.从囊性纤维化患者中分离的细菌和临床分离株。添加β-内酰胺酶抑制剂阿维巴坦可抑制T405耐药性的发展。T405在小鼠中表现出良好的药代动力学特征，且无毒性，进一步证明了其临床潜力。
β-lactams are the most widely used antibiotic class to treat bacterial infections in humans. Mycobacteroides abscessus is an emerging pulmonary pathogen resistant to most antibiotics, including penicillins and cephalosporins. With no current FDA-approved treatment and cure rates <50%, there is a pressing need for effective therapies. Here we report T405, a new β-lactam of the penem subclass that exhibits potent activity against M. abscessus and a panel of drug-resistant strains isolated from cystic fibrosis patients. Additionally, in combination with the β-lactamase inhibitor avibactam, the rate of spontaneous resistance of M. abscessus to T405 approached the limit of detection. Lastly, we show the favorable pharmacokinetic profile of T405 in mice and the absence of toxicity at elevated dosage, which support the clinical potential of this compound. Batchelder et al. report a new penem class antibiotic, T405, which exhibits potent activity against M. abscessus and clinical isolates from cystic fibrosis patients. The development of resistance to T405 is inhibited with the addition of a β-lactamase inhibitor, avibactam. Its clinical potential is further demonstrated by T405 displaying a favourable pharmacokinetic profile in mice with an absence of toxicity.
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影响因子：
4.9
作者：
Lefebvre, Anne-Laure;Le Moigne, Vincent;Mainardi, Jean-Luc
通讯作者：
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影响因子：
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