State University of New York Upstate University Hospital, Syracuse, NY, USA.
Binghamton University School of Pharmacy and Pharmaceutical Sciences, Binghamton, NY, USA.
J Antimicrob Chemother. 2021 May 12;76(6):1379-1391. doi: 10.1093/jac/dkab015.
Cefiderocol is a novel siderophore cephalosporin that forms a complex with extracellular free ferric iron, which leads to transportation across the outer cell membrane to exert its bactericidal activity through cell wall synthesis inhibition. This pharmacological property has rendered cefiderocol active against several clinically relevant MDR Gram-negative bacteria as evidenced by several in vitro and in vivo studies. Cefiderocol was first approved by the US FDA on 14 November 2019 for the treatment of complicated urinary tract infections. On 28 September 2020, cefiderocol was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The FDA-approved indications are based on clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In APEKS-cUTI, cefiderocol demonstrated non-inferiority to imipenem/cilastatin for the treatment of complicated urinary tract infection caused by MDR Gram-negative bacteria. In APEKS-NP, cefiderocol demonstrated non-inferiority to meropenem for treatment of nosocomial pneumonia. However, in CREDIBLE-CR, higher all-cause mortality was observed with cefiderocol compared with best available therapy for the treatment of severe infections caused by Gram-negative bacteria, primarily in the subset of patients with Acinetobacter spp. infections. Several case reports/series have demonstrated clinical success with cefiderocol for a variety of severe infections. The purpose of this article is to review available data on the mechanism of action, in vitro and in vivo data, pharmacokinetics, pharmacodynamics, susceptibility testing, efficacy and safety of cefiderocol to address its role in therapy.
头孢地尔是一种新型的铁载体头孢菌素，它与细胞外游离的三价铁形成复合物，从而通过抑制细胞壁合成将其运输穿过外细胞膜发挥杀菌作用。这种药理学特性使头孢地尔对几种临床相关的耐多药革兰氏阴性菌具有活性，这已被多项体外和体内研究证实。2019 年 11 月 14 日，美国食品和药物管理局（FDA）首次批准头孢地尔用于治疗复杂性尿路感染。2020 年 9 月 28 日，头孢地尔被批准用于治疗医院获得性细菌性肺炎和呼吸机相关性细菌性肺炎。FDA 批准的适应证是基于 APEKS-cUTI、APEXS-NP 和 CREDIBLE-CR 试验的临床数据。在 APEKS-cUTI 中，头孢地尔在治疗由耐多药革兰氏阴性菌引起的复杂性尿路感染方面与亚胺培南/西司他丁不劣效。在 APEKS-NP 中，头孢地尔在治疗医院获得性肺炎方面与美罗培南不劣效。然而，在 CREDIBLE-CR 中，与严重革兰氏阴性菌感染的最佳治疗方法相比，头孢地尔治疗导致的全因死亡率更高，主要发生在不动杆菌属感染的患者亚组中。一些病例报告/系列已经证明头孢地尔在各种严重感染中的临床疗效。本文的目的是回顾头孢地尔的作用机制、体外和体内数据、药代动力学、药效学、药敏试验、疗效和安全性方面的现有数据，以探讨其在治疗中的作用。
