Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
Expert Rev Anti Infect Ther. 2022 Aug;20(8):1077-1094. doi: 10.1080/14787210.2022.2071701. Epub 2022 May 10.
Carbapenem-resistant (CR) infections constitute a serious clinical threat globally. Patients are often critically ill and/or immunocompromised. Antibiotic options are limited and are currently centered on beta-lactam-beta-lactamase inhibitor (BL-BLI) combinations and the siderophore cephalosporin cefiderocol.
This article reviews the mechanisms of resistance and their potential impact on the activity of current treatment options, along with evidence for the clinical efficacy of BL-BLI combinations in infections, some of which specifically target infections due to CR organisms. The preclinical and clinical evidence supporting cefiderocol as a treatment option for involving infections is also reviewed.
Cefiderocol is active against most known mechanisms mediating carbapenem resistance. It is stable against different serine- and metallo-beta-lactamases, and, due to its iron channel-dependent uptake mechanism, is not impacted by porin channel loss. Furthermore, the periplasmic level of cefiderocol is not affected by upregulated efflux pumps. The potential for on-treatment resistance development currently appears to be low, although more clinical data are required. Information from surveillance programs, real-world compassionate use, and clinical studies demonstrate that cefiderocol is an important treatment option for CR infections.
全球范围内,碳青霉烯类耐药(CR)感染构成了严重的临床威胁。此类患者通常病情严重,且/或免疫功能低下。可供选择的抗生素十分有限,目前主要集中于β-内酰胺类-β-内酰胺酶抑制剂(BL-BLI)联合制剂和铁载体头孢菌素类药物头孢地尔。
本文综述了耐药机制及其对当前治疗选择的潜在影响,还探讨了 BL-BLI 联合制剂在治疗感染方面的临床疗效证据,其中部分药物专门针对由 CR 病原体引起的感染。此外,还回顾了头孢地尔作为治疗涉及 CR 病原体感染的治疗选择的临床前和临床证据。
头孢地尔对大多数已知介导碳青霉烯类耐药的机制均具有活性。它对不同丝氨酸和金属β-内酰胺酶具有稳定性,并且由于其铁离子通道依赖性摄取机制,不受孔道缺失的影响。此外,头孢地尔的周质水平不受上调的外排泵的影响。目前,治疗过程中耐药发展的可能性似乎较低,但仍需要更多的临床数据。来自监测计划、真实世界同情用药和临床研究的信息表明,头孢地尔是治疗 CR 感染的重要选择。