耐碳青霉烯类鲍曼不动杆菌(CRAB)已被世界卫生组织列为需要紧急新抗生素治疗选择的关键病原体类别。头孢地洛,第一个批准的铁载体头孢菌素,被设计用于治疗CR革兰氏阴性病原体,特别是非发酵物种鲍曼不动杆菌和铜绿假单胞菌。头孢地洛对丝氨酸和金属β-内酰胺酶的水解大多稳定,这是导致碳青霉烯耐药的主要原因。这篇综述整理了关于体外活性的现有证据,药代动力学/药效学,头孢地洛的疗效和安全性,并概述了其目前在CRAB感染管理中的作用。体外监测数据显示头孢地洛对CRAB分离株的敏感性>90%,以及与指南中推荐的多种抗生素的体外协同作用。头孢地洛单药治疗CRAB感染的临床疗效已在描述性,开放标签可信CR和非劣效性,双盲APEKS-NP随机临床试验和有潜在健康问题患者的实际病例。迄今为止,鲍曼不动杆菌对头孢地洛的耐药性在治疗中发展的频率似乎很低,但强烈建议进行监测。在目前的中重度CRAB感染治疗指南中,推荐头孢地洛用于其他抗生素失败的感染,并与其他活性抗生素联合使用。体内临床前数据支持舒巴坦或阿维巴坦与头孢地洛的组合可增强功效并抑制对头孢地洛的耐药性的出现。联合治疗在临床环境中的益处尚未在前瞻性研究中确定。
Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa. Cefiderocol is mostly stable against hydrolysis by serine β-lactamases and metallo-β-lactamases, which are leading causes of carbapenem resistance. This
review collates the available evidence on the in vitro activity, pharmacokinetics/pharmacodynamics, and efficacy and safety of cefiderocol, and outlines its current role in the management of CRAB infections. In vitro surveillance data show susceptibility rates of >90% for cefiderocol against CRAB isolates as well as in vitro synergism with a variety of antibiotics recommended in guidelines. Clinical efficacy of cefiderocol monotherapy against CRAB infections has been demonstrated in the descriptive, open-label CREDIBLE-CR and the non-inferiority, double-blind APEKS-NP randomised clinical trials as well as in real-world cases in patients with underlying health problems. To date, the frequency of on-therapy development of cefiderocol resistance in A. baumannii appears to be low, but monitoring is highly recommended. Within current treatment guidelines for moderate-to-severe CRAB infections, cefiderocol is recommended for infections in which other antibiotics failed and in combination with other active antibiotics. In vivo pre-clinical data support the combination of sulbactam or avibactam with cefiderocol to enhance efficacy and to suppress the emergence of cefiderocol resistance. The benefit of combination therapy in the clinical setting is yet to be determined in prospective studies.