Therapeutic options for the treatment of infections owing to multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol is a novel siderophore cephalosporin with activity against Gram-negative pathogens, including many multidrug-resistant strains. The activity of cefiderocol was examined against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii that included (1) a recent surveillance collection of clinical isolates, (2) a collection of carbapenem-resistant isolates from a previous surveillance study, and (3) a collection of well-characterized isolates. Susceptibility testing for cefiderocol was performed with iron-depleted cation-adjusted Mueller–Hinton broth. Cefiderocol minimum inhibitory concentrations (MICs) were correlated with resistance mechanisms in the well-characterized isolates. For the Enterobacterales, including a collection of KPC-possessing Klebsiella pneumoniae, cefiderocol MICs were all ≤4 mg/L. Cefiderocol MICs were two- to fourfold higher in cephalosporin-resistant isolates. For K. pneumoniae, MICs did not correlate with expression of genes encoding porins or efflux systems. For P. aeruginosa, >99% of isolates were inhibited by ≤4 mg/L, including the collection of carbapenem-resistant isolates. For P. aeruginosa, cefiderocol activity was not affected by expression of ampC, oprD, or several efflux systems. All the surveillance isolates of A. baumannii, and 88% of the collection of carbapenem-resistant isolates, had cefiderocol MICs ≤4 mg/L. MICs were twofold higher in A. baummannii isolates with proven extended-spectrum beta-lactamases, and cefiderocol activity did not correlate with expression of efflux systems. Cefiderocol demonstrated potent activity against important nosocomial pathogens. Continued development of this agent as a therapeutic option against multidrug-resistant bacteria should be encouraged.

中文翻译：

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头孢地洛尔对纽约市医疗中心特有的肠杆菌，铜绿假单胞菌和鲍曼不动杆菌的活性。

由于多重耐药的革兰氏阴性病原体引起的感染的治疗选择常常受到限制。头孢地洛尔是一种新型的铁载体头孢菌素，对革兰氏阴性病原体具有活性，包括许多耐多药菌株。检查头孢地洛尔对肠杆菌，铜绿假单胞菌和鲍曼不动杆菌的活性其中包括（1）最近监测到的临床分离株，（2）来自先前监测研究的对碳青霉烯耐药的分离株，以及（3）特征明确的分离株。用贫铁阳离子调节的Mueller-Hinton肉汤进行头孢地洛尔的药敏试验。在表征良好的分离物中，头孢地洛尔的最低抑菌浓度（MIC）与耐药机制相关。对于肠杆菌，包括具有KPC的肺炎克雷伯菌，所有的头孢地洛尔MIC均≤4mg / L。在头孢菌素耐药菌株中，头孢地洛尔的MICs高2-4倍。对于肺炎克雷伯菌，MIC与编码孔蛋白或外排系统的基因表达无关。对于铜绿假单胞菌，> 99％的分离物被≤4mg / L抑制，包括收集有耐碳青霉烯的分离物。对于铜绿假单胞菌，头孢地洛尔的活性不受ampC，oprD或几种外排系统表达的影响。鲍曼不动杆菌的所有监测分离株，以及耐碳青霉烯分离株的88％收集到的头孢地洛尔MIC≤4 mg / L。鲍曼不动杆菌中的MIC高出两倍分离物具有广谱的β-内酰胺酶，头孢地洛尔的活性与外排系统的表达无关。头孢地洛尔显示出对重要的医院病原体的有效活性。应鼓励继续开发这种药物，作为对抗多重耐药细菌的治疗选择。