Department of Internal Medicine, Division of Infectious Diseases, Houston Methodist Hospital, Houston, TX, USA.
Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX, USA.
Nat Rev Microbiol. 2024 Oct;22(10):598-616. doi: 10.1038/s41579-024-01054-w. Epub 2024 Jun 3.
The rise of antibiotic resistance and a dwindling antimicrobial pipeline have been recognized as emerging threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria for which effective therapies were rapidly needed. Now, entering the third decade of the twenty-first century, and despite the introduction of several new antibiotics and antibiotic adjuvants, such as novel β-lactamase inhibitors, these organisms continue to represent major therapeutic challenges. These bacteria share several key biological features, including adaptations for survival in the modern health-care setting, diverse methods for acquiring resistance determinants and the dissemination of successful high-risk clones around the world. With the advent of next-generation sequencing, novel tools to track and combat the spread of these organisms have rapidly evolved, as well as renewed interest in non-traditional antibiotic approaches. In this Review, we explore the current epidemiology and clinical impact of this important group of bacterial pathogens and discuss relevant mechanisms of resistance to recently introduced antibiotics that affect their use in clinical settings. Furthermore, we discuss emerging therapeutic strategies needed for effective patient care in the era of widespread antimicrobial resistance.
抗生素耐药性的上升和抗菌药物研发管线的枯竭已被认为是对公共卫生的新兴威胁。ESKAPE 病原体——屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属——最初被确定为关键的多重耐药细菌,需要迅速开发有效的治疗方法。如今,进入 21 世纪第三个十年,尽管引入了几种新的抗生素和抗生素佐剂,如新型β-内酰胺酶抑制剂,但这些病原体仍然是主要的治疗挑战。这些细菌具有一些关键的生物学特征,包括适应现代医疗环境中的生存、获得耐药决定因素的多种方法以及成功的高危克隆在全球的传播。随着下一代测序技术的出现,追踪和对抗这些病原体传播的新工具迅速发展起来,同时也重新关注非传统的抗生素方法。在这篇综述中,我们探讨了这组重要的细菌病原体的当前流行病学和临床影响,并讨论了影响其在临床环境中使用的最近引入的抗生素的相关耐药机制。此外,我们还讨论了在广泛存在抗菌药物耐药的时代,为有效治疗患者所需的新兴治疗策略。