Abstract:
Cefiderocol is a novel synthetic siderophore-conjugated antibiotic that hijacks the bacterial iron transport systems facilitating drug entry into cells, achieving high periplasmic concentrations. This systematic review analyzed the currently available literature on cefiderocol. It summarized in vitro susceptibility data, in vivo antimicrobial activity, pharmacokinetics/pharmacodynamics (PK/PD), clinical efficacy, safety and resistance mechanisms of cefiderocol. Cefiderocol has potent in vitro and in vivo activity against multidrug-resistant (MDR) Gram-negative bacteria, including carbapenem-resistant isolates. But New Delhi Metallo-β-lactamase (NDM)- positive isolates showed significantly higher MICs than other carbapenemase-producing Enterobacterales, with a susceptible rate of 83.4% for cefiderocol. Cefiderocol is well-tolerated, and the PK/PD target values can be achieved using a standard dose regimen or adjusted doses according to renal function. Clinical trials demonstrated that cefiderocol was non-inferiority to the comparator drugs in treating complicated urinary tract infection and nosocomial pneumonia. Case reports and series showed that cefiderocol was a promising therapeutic agent in carbapenem-resistant infections. However, resistant isolates and reduced susceptibility during treatment to cefiderocol have already been reported. In conclusion, cefiderocol is a promising powerful weapon for treating MDR recalcitrant infections.
摘要:
Cefiderocol是一种新型的合成铁载体结合的抗生素,可以劫持细菌铁转运系统,促进药物进入细胞,实现高周质浓度。本系统综述分析了目前可用的头孢地洛的文献。它总结了体外药敏数据,体内抗菌活性,药代动力学/药效学(PK/PD),临床疗效,头孢地洛的安全性和抗性机制。头孢地洛对多重耐药(MDR)革兰氏阴性菌具有有效的体外和体内活性,包括耐碳青霉烯的分离株。但新德里金属-β-内酰胺酶(NDM)-阳性分离株显示出显著高于其他产生碳青霉烯酶的肠杆菌,头孢地洛的易感率为83.4%。头孢地洛有良好的耐受性,和PK/PD目标值可以使用标准剂量方案或根据肾功能调整的剂量来实现。临床试验表明,头孢地洛在治疗复杂性尿路感染和医院获得性肺炎方面与比较药物相比具有非劣效性。病例报告和系列显示头孢地洛是碳青霉烯类耐药感染的有前途的治疗剂。然而,已经报道了耐药分离株和治疗期间对头孢地洛的敏感性降低。总之,头孢地洛是治疗MDR难治性感染的有前途的有力武器。