The objective of this study was to assess the susceptibility of cefiderocol against multidrug-resistant carbapenemase-producing and nonproducing bacteria. The panel comprised 182 isolates of the order Enterobacterales, and 40 strains of Pseudomonas aeruginosa. Antimicrobial susceptibility testing has been performed using broth microdilution method according to the European Committee on Antimicrobial Susceptibility Testing recommendations. Mass spectrometry matrix-assisted laser desorption/ionization-time of flight mass spectrometry and carbapenemase-producing test were used to verify the presence of carbapenemases in clinical isolates. The genetic expression of single carbapenemases (blaKPC, blaOXA-48, blaNDM, blaVIM, blaIMP, blaGES) was determined by real-time polymerase chain reaction. Cefiderocol exhibited a good activity against the majority of strains tested in this study. Altogether, growth of 81.9% (n = 149) strains of the order Enterobacterales and 77.5% (n = 31) of P. aeruginosa isolates were inhibited at minimal inhibitory concentration (MIC) ≤2 mg/L. Values MIC50/MIC90 were 0.5/8 mg/L for enterobacteria, and 1/8 mg/L for P. aeruginosa. One isolate (Klebsiella pneumoniae) harboring two carbapenemases (blaOXA-48, blaNDM) had cefiderocol MIC 0.5 mg/L. In enterobacteria resistant to cefiderocol, blaNDM carbapenemase prevailed (43.3%, n = 29), followed by blaOXA-48 (31.3%, n = 21) and blaKPC (4.5%, n = 3). blaIMP (n = 8) and blaVIM (n = 1) metallo-β-lactamases dominated in cefiderocol-resistant P. aeruginosa (n = 9) isolates. Very good susceptibility (100%) to this drug showed blaGES-positive strains of P. aeruginosa (n = 8) and isolates resistant to meropenem without confirmed carbapenemase gene (n = 10). In this study, cefiderocol demonstrated potent activity against important nosocomial pathogens, therefore, therapeutic options of this drug against multidrug-resistant bacteria should be considered.

中文翻译：

---

头孢地罗可对抗碳青霉烯类耐药肠杆菌和铜绿假单胞菌的体外活性。

本研究的目的是评估头孢菌素对产生和不产生碳青霉烯酶的多重耐药细菌的敏感性。该组包含 182 个肠杆菌目分离株和 40 个铜绿假单胞菌菌株。根据欧洲抗菌药物敏感性测试委员会的建议，使用肉汤微量稀释法进行抗菌药物敏感性测试。采用质谱基质辅助激光解吸/电离飞行时间质谱和碳青霉烯酶产生试验来验证临床分离株中碳青霉烯酶的存在。通过实时聚合酶链式反应测定单一碳青霉烯酶（blaKPC、blaOXA-48、blaNDM、blaVIM、blaIMP、blaGES）的基因表达。头孢地考对本研究中测试的大多数菌株表现出良好的活性。总共，81.9% (n = 149) 肠杆菌目的菌株和 77.5% (n = 31) 铜绿假单胞菌分离株的生长在最低抑制浓度 (MIC) ≤ 2 mg/L 时受到抑制。肠杆菌的 MIC50/MIC90 值为 0.5/8 mg/L，铜绿假单胞菌的 MIC50/MIC90 值为 1/8 mg/L。含有两种碳青霉烯酶（blaOXA-48、blaNDM）的一株分离株（肺炎克雷伯菌）的头孢地罗 MIC 为 0.5 mg/L。在对头孢菌素耐药的肠杆菌中，blaNDM 碳青霉烯酶占主导地位（43.3%，n = 29），其次是 blaOXA-48（31.3%，n = 21）和 blaKPC（4.5%，n = 3）。blaIMP (n = 8) 和 blaVIM (n = 1) 金属-β-内酰胺酶在头孢菌素耐药铜绿假单胞菌 (n = 9) 分离株中占主导地位。对该药物具有非常好的敏感性（100%），表明 blaGES 阳性铜绿假单胞菌菌株（n = 8）和对美罗培南耐药但未确认碳青霉烯酶基因的分离株（n = 10）。在这项研究中，头孢地考证明了对重要的医院病原体的有效活性，因此，应考虑该药物针对多重耐药细菌的治疗选择。