In vitro antibacterial activity of cefiderocol against recent multidrug-resistant carbapenem-nonsusceptible Enterobacterales isolates

• Published in: Diagnostic microbiology and infectious disease 2022-05, Vol.103 (1), p.115651-115651, Article 115651
• Main Authors: Zhang, Qingyu, Neidig, Nicholas, Chu, Ting-Yu, Divoky, Cameron, Carpenter, Jessica, Lee-Hsiao, Cristian, Threatt, Hillary, Sultana, Rasheda, Bush, Karen
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Azabicyclo Compounds; beta-Lactamases - genetics; Carbapenemase; Carbapenems - pharmacology; Cefiderocol; Cephalosporins - pharmacology; Drug Combinations; Enterobacterales; Humans; Meropenem - pharmacology; Microbial Sensitivity Tests; Siderophore
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2022.115651

Cefiderocol, a siderophore-containing cephalosporin with broad-spectrum antimicrobial activity against many β-lactam-resistant Gram-negative bacteria, was tested by broth microdilution against 104 carbapenem-non-susceptible Enterobacterales clinical isolates from 2011 to 2018. Carbapenemase identification was determined using PCR followed by targeted gene sequencing or whole genome sequencing (WGS). All isolates were multidrug-resistant, 89.4% (93/104) and produced a serine (KPC or SME) carbapenemase, with as many as four β-lactamases present. A VIM-1 or NDM-1 metallo-β-lactamase was confirmed in 6.7% of the isolates (N = 5 and 2, respectively). All isolates were susceptible to cefiderocol, unlike the comparator agents. Susceptibility for comparators ranged from 24.0% for meropenem to 91.3%, 92.3% and 96.1% for imipenem-relebactam, ceftazidime-avibactam and meropenem-vaborbactam, respectively; 48.1%, 75.2% and 79.8% of the isolates were susceptible to omadacycline, colistin and eravacycline, respectively. Two isolates with cefiderocol MICs of 2 mg/L had mutations or deletions of the iron transport genes fhuA/E or fepA, as determined by WGS.