Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA.
Clin Infect Dis. 2024 Jul 19;79(1):33-42. doi: 10.1093/cid/ciae048.
Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of β-lactamases. The early β-lactamase inhibitors (BLIs) are characterized by spectra limited to class A β-lactamases and ineffective against carbapenemases and most extended spectrum β-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC). These BL/BLI combination drugs, avibactam/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven to be indispensable tools in this effort. However, non-KPC mechanisms of resistance are rising in prevalence and increasingly challenging to treat. It is critical for clinicians to understand the unique spectra of these BL/BLIs with respect to non-KPC CRO. In Part 1of this 2-part series, we describe the non-KPC attributes of the newer BL/BLIs with a focus on utility against Enterobacterales and Pseudomonas aeruginosa.
由于β-内酰胺酶的进化和传播，革兰氏阴性抗生素耐药性继续成为一个全球性问题。早期的β-内酰胺酶抑制剂（BLIs）的特点是光谱仅限于 A 类β-内酰胺酶，对碳青霉烯酶和大多数扩展谱β-内酰胺酶无效。为了满足这一治疗需求，开发了新型的 BLIs，旨在治疗产生碳青霉烯酶、耐碳青霉烯的生物体（CRO），特别是针对肺炎克雷伯氏菌碳青霉烯酶（KPC）。这些 BL/BLI 联合药物，阿维巴坦/阿维巴坦、美罗培南/瓦博巴坦和亚胺培南/雷利巴坦，已被证明是这方面不可或缺的工具。然而，非 KPC 耐药机制的流行率正在上升，并且越来越难以治疗。临床医生了解这些 BL/BLIs 针对非 KPC CRO 的独特光谱非常重要。在这两部分系列的第 1 部分中，我们描述了新型 BL/BLI 的非 KPC 属性，重点是针对肠杆菌科和铜绿假单胞菌的效用。
