Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, Public Health England, London, United Kingdom
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, Public Health England, London, United Kingdom.
Antimicrob Agents Chemother. 2020 Nov 17;64(12). doi: 10.1128/AAC.01582-20.
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 , 111 of , and 99 of , 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 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 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 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 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 isolates with metallo-β-lactamases (MBLs) and serine carbapenemase, respectively, indicating incomplete β-lactamase stability.
头孢他啶是一种含有儿茶酚的 3' 取代基的母体噁唑烷酮头孢菌素。我们使用缺铁 Mueller-Hinton 肉汤评估了其对革兰氏阴性菌的 MIC。该小组包括 305 株 、111 株 、99 株 ，所有这些菌株均因碳青霉烯类耐药和对其他药物的多药耐药而被选择。在 2 和 4μg/ml 时，头孢他啶分别抑制了所有 305 株测试菌株的 78.7%和 92.1%，对除 NDM 酶（在 2μg/ml 时抑制率为 41.0%，在 4μg/ml 时抑制率为 72.1%）或扩展谱β-内酰胺酶（ESBL）和孔蛋白缺失（在 2μg/ml 时抑制率为 61.5%，在 4μg/ml 时抑制率为 88.5%）以外的所有碳青霉烯类耐药模式的菌株的抑制率为 80-100%。头孢他啶在 2 和 4μg/ml 时也分别抑制了所有 305 株 305 株的 81.1%和 86.5%，对 VIM、IMP、GES 或 VEBβ-内酰胺酶的菌株的抑制率为 80-100%，而对 NDM（在 2μg/ml 时抑制率为 45.5%，在 4μg/ml 时抑制率为 72.7%）和 PER（在 2μg/ml 时抑制率为 66.7%，在 4μg/ml 时抑制率为 73.3%）酶的菌株的抑制率略低；63.3%的 菌株在 FDA 的 1μg/ml 折点被抑制。最后，头孢他啶在 2 和 4μg/ml 时分别抑制了 80.8%和 88.9%的 菌株，对 OXA-51 样、-23、-24 或 -58 酶的菌株的抑制率>85%，对 NDM 碳青霉烯酶的菌株的抑制率为 50%（在 2μg/ml 时）和 80%（在 4μg/ml 时）。 头孢他啶对含金属β-内酰胺酶（MBLs）和丝氨酸碳青霉烯酶的菌株的稳定性较弱，分别与二吡啶羧酸和阿维巴坦弱增效。
