Cefiderocol is a parenteral siderophore cephalosporin with a catechol-containing 3′ substituent. We evaluated its MICs against Gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The panel comprised 305 isolates of Enterobacterales, 111 of Pseudomonas aeruginosa, and 99 of Acinetobacter baumannii, all selected for carbapenem resistance and multidrug resistance to other agents. At 2 and 4 μg/ml, cefiderocol inhibited 78.7 and 92.1%, respectively, of all Enterobacterales isolates tested, with rates of 80 to 100% for isolates with all modes of carbapenem resistance except NDM enzymes (41.0% inhibited at 2 μg/ml and 72.1% at 4 μg/ml) or combinations of extended-spectrum β-lactamase (ESBL) and porin loss (61.5% inhibited at 2 μg/ml and 88.5% at 4 μg/ml). Cefiderocol also inhibited 81.1 and 86.5% of all P. aeruginosa isolates at 2 and 4 μg/ml, respectively, with rates of 80 to 100% for isolates with VIM, IMP, GES, or VEB β-lactamases and slightly lower rates for those with NDM (45.5% at 2 μg/ml and 72.7% at 4 μg/ml) and PER (66.7% at 2 μg/ml and 73.3% at 4 μg/ml) enzymes; 63.3% of P. aeruginosa isolates were inhibited at the FDA’s 1-μg/ml breakpoint. Lastly, cefiderocol at 2 and 4 μg/ml inhibited 80.8 and 88.9% of the A. baumannii isolates, respectively, with rates of >85% for isolates with OXA-51-like, -23, -24, or -58 enzymes and 50% at 2 μg/ml and 80% at 4 μg/ml for those with NDM carbapenemases. Dipicolinic acid and avibactam weakly potentiated cefiderocol against Enterobacterales isolates with metallo-β-lactamases (MBLs) and serine carbapenemase, respectively, indicating incomplete β-lactamase stability.

中文翻译：

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头孢菌素（一种铁载体头孢菌素）对多重耐药革兰氏阴性菌的体外活性。


头孢地考是一种肠胃外铁载体头孢菌素，具有含儿茶酚的 3' 取代基。我们使用贫铁 Mueller-Hinton 肉汤评估了其对革兰氏阴性菌的 MIC。该小组包括 305 株肠杆菌、111 株铜绿假单胞菌和 99 株鲍曼不动杆菌，所有这些均因碳青霉烯类耐药性和对其他药物的多药耐药性而被选择。 2 μg/ml 和 4 μg/ml 时，头孢地罗可分别抑制所有测试的肠杆菌分离株的 78.7% 和 92.1%，对于除 NDM 酶以外的所有碳青霉烯类耐药模式的分离株，抑制率为 80% 至 100%（2 μg/ml 时抑制 41.0%） 4 μg/ml 时抑制 72.1%）或超广谱 β-内酰胺酶 (ESBL) 和孔蛋白损失的组合（2 μg/ml 时抑制 61.5%，4 μg/ml 时抑制 88.5%）。头孢地考还分别在 2 和 4 μg/ml 浓度下抑制 81.1% 和 86.5% 的铜绿假单胞菌分离株，对于含有 VIM、IMP、GES 或 VEB β-内酰胺酶的分离株，抑制率为 80% 至 100%，对于那些含有 VIM、IMP、GES 或 VEB β-内酰胺酶的分离株，抑制率略低。使用 NDM（2 μg/ml 时为 45.5%，4 μg/ml 时为 72.7%）和 PER（2 μg/ml 时为 66.7%，4 μg/ml 时为 73.3%）酶； 63.3% 的铜绿假单胞菌分离株在 FDA 的 1 μg/ml 断点处受到抑制。最后，2 和 4 μg/ml 的头孢地考分别抑制 80.8% 和 88.9% 的鲍曼不动杆菌分离株，对于具有 OXA-51 样、-23、-24 或 -58 酶的分离株，抑制率 >85%。对于使用 NDM 碳青霉烯酶的患者，2 μg/ml 时为 50%，4 μg/ml 时为 80%。吡啶二羧酸和阿维巴坦分别对带有金属-β-内酰胺酶（MBL）和丝氨酸碳青霉烯酶的肠杆菌分离株具有弱增强作用，表明头孢德罗科尔对β-内酰胺酶的稳定性不完全。