Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medicine University, Taipei, Taiwan.
Drugs. 2019 May;79(7):705-714. doi: 10.1007/s40265-019-01112-1.
A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. Most of these antibiotics display good in vitro activity against the producers of Ambler class A, C, and D β-lactamase, although avibactam and vaborbactam are not active in vitro against metallo-β-lactamase (MβL) enzymes. Nevertheless, in vitro efficacy against the producers of some or all class B enzymes (New Delhi MβL, Verona integron-encoded MβL, etc) has been shown with cefepime-zidebactam, aztreonam-avibactam, VNRX-5133, cefiderocol, plazomicin, and eravacycline. As of Feburary 2019, drugs approved for treatment of some CRE-related infections by the US Food and Drug Administration included ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, and eravacycline. Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.
革兰氏阴性菌（尤其是耐碳青霉烯类肠杆菌科细菌[CRE]、耐碳青霉烯类铜绿假单胞菌和广泛耐药鲍曼不动杆菌）的耐药趋势逐渐上升，对全球医疗保健系统构成了巨大威胁。在过去十年中，许多制药公司投入了大量资源来开发针对 XDR 革兰氏阴性病原体的新型强效抗生素，尤其是针对 CRE 的抗生素。这些针对 CRE 菌株的新型抗生素中的一些是β-内酰胺/β-内酰胺酶抑制剂组合药物，而另一些则属于非β-内酰胺类药物。这些抗生素中的大多数对 Ambler 类 A、C 和 D 型β-内酰胺酶的产生者表现出良好的体外活性，尽管阿维巴坦和沃巴坦对金属β-内酰胺酶（MβL）酶没有体外活性。然而，头孢吡肟-他唑巴坦、氨曲南-阿维巴坦、VNRX-5133、头孢地尔、硫酸帕拉米韦和依拉环素已被证明对某些或所有 B 类酶（新德里 MβL、 Verona 整合子编码 MβL 等）的产生者具有体外疗效。截至 2019 年 2 月，美国食品和药物管理局批准用于治疗某些 CRE 相关感染的药物包括头孢他啶-阿维巴坦、美罗培南-沃巴坦、硫酸帕拉米韦和依拉环素。虽然达福沙星对产超广谱和 AmpC 类β-内酰胺酶的肠杆菌科具有活性，但对 CRE 没有体外活性。米雷帕丹被证明对耐碳青霉烯类和多粘菌素耐药的铜绿假单胞菌菌株具有特异性活性。尽管新型抗生素的开发取得了成功，但在医院中严格实施抗生素管理政策，结合使用经过验证的表型检测和新型多重 PCR 方法来检测最常见的β-内酰胺酶/碳青霉烯酶，对于针对 CRE 开具有效抗生素和减少因 CRE 产生的耐药负担非常重要。
