头孢地尔：新型铁载体头孢菌素抗多重耐药革兰阴性杆菌感染

Cefiderocol:a novel siderophore cephalosporin against multi-drug resistant Gram-negative bacilli infections

摘要:

抗菌药物耐药是目前全世界面临的重要公共卫生问题之一，亟需开发有效的广谱抗菌药物以应对多重耐药革兰阴性杆菌的感染。头孢地尔是日本Shionogi公司开发的新型铁载体头孢菌素类抗菌药物。该药物对碳青霉烯耐药的肠杆菌目细菌(carbapenem resistant Enterobacterales,CRE)、铜绿假单胞菌、鲍曼不动杆菌和嗜麦芽窄食单胞菌等具有广谱强效的抗菌活性。该药物克服了革兰阴性杆菌因外膜孔道蛋白表达量下调和主动外排泵表达量上调产生的耐药性，并对丝氨酸酶和金属碳青霉烯酶具有较好的稳定性。该药可用于治疗由革兰阴性杆菌引起的复杂性尿路感染(包括肾盂肾炎)、院内获得性肺炎和呼吸机相关性肺炎。文中通过汇总头孢地尔的化学结构、抗菌作用机制、体外抗菌活性、药代动力学、药效学和临床治疗等信息，展现头孢地尔作为新型铁载体头孢菌素在治疗多重耐药革兰阴性杆菌感染中的应用前景。

Abstract:

Antimicrobial resistance is one of the critical public health issues in the world.There is an urgent need to develop effective broad-spectrum antibiotics to treat the infection of multi-drug resistant Gram-negative bacilli.Cefiderocol,developed by the Shionogi Inc.in Japan,is a new type of iron carrier cephalosporin antibiotics,which overcomes the drug resistance of Gram-negative bacilli due to the down-regulation of outer membrane pore protein and the up-regulation of efflux pump,and has good stability to serine-and metallo-carbapenemases.This drug has a broad spectrum and strong antibacterial activity against carbapenem-resistant Enterobacteriaceae (CRE),Pseudomonas aeruginosa,Acinetobacter baumannii,and Stenotrophomonas maltophilia.Cefiderocol can be used to treat complex urinary tract infections (including pyelonephritis),hospital-acquired pneumonia,and ventilator-associated pneumonia.By summarizing the chemical structure,antibacterial mechanism,in vitro antibacterial activity,pharmacokinetics,pharmacodynamics,and clinical treatment of cefiderocol,this review shows the application potential of cefiderocol as a new iron carrier cephalosporin in the treatment of multi-drug resistant Gram-negative bacilli infections.