Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0217120. doi: 10.1128/AAC.02171-20.
Bacterial resistance to carbapenem agents has reached alarming levels. Accordingly, collaborative efforts between national and international organizations and the pharmaceutical industry have led to an impressive expansion of commercially available β-lactam agents in recent years. No available agent comes close to the broad range of activity afforded by cefiderocol, a novel siderophore-cephalosporin conjugate. The novelty of and need for cefiderocol are clear, but available clinical data are conflicting, leaving infectious diseases specialists puzzled as to when to prescribe this agent in clinical practice. After a brief overview of cefiderocol pharmacokinetics and pharmacodynamics, safety data, cefiderocol susceptibility testing, and putative mechanisms of cefiderocol resistance, this review focuses on determining cefiderocol's role in the management of specific pathogens, including carbapenem-resistant Acinetobacter baumannii complex, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant , and less commonly identified glucose-nonfermenting organisms such as Stenotrophomonas maltophilia, species, and species. Available preclinical, clinical trial, and postmarketing data are summarized for each organism, and each section concludes with our opinions on where to position cefiderocol as a clinical therapeutic.
细菌对碳青霉烯类药物的耐药性已达到令人震惊的水平。因此,近年来,国家和国际组织以及制药行业之间的合作努力使得商业上可用的β-内酰胺类药物得到了显著扩展。没有任何可用的药物能与头孢他啶-多粘菌素类药物相媲美,这是一种新型的铁载体头孢菌素结合物。头孢他啶的新颖性和必要性是显而易见的,但现有的临床数据存在冲突,这让传染病专家在临床实践中何时使用该药物感到困惑。在简要概述头孢他啶的药代动力学和药效学、安全性数据、头孢他啶药敏试验和头孢他啶耐药的可能机制后,本综述重点讨论了确定头孢他啶在管理特定病原体中的作用,包括耐碳青霉烯类鲍曼不动杆菌复合群、耐碳青霉烯类铜绿假单胞菌、耐碳青霉烯类肠杆菌科细菌以及不太常见的葡萄糖非发酵菌,如嗜麦芽窄食单胞菌、洋葱伯克霍尔德菌和产酸克雷伯菌。总结了每种病原体的临床前、临床试验和上市后数据,每个部分都总结了我们对头孢他啶在临床治疗中的定位的看法。