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

Qingyu Zhang; Nicholas Neidig; Ting-Yu Chu; Cameron Divoky; Jessica Carpenter; Cristian Lee-Hsiao; Hillary Threatt; Rasheda Sultana; Karen Bush

doi:10.1016/j.diagmicrobio.2022.115651

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

Diagn Microbiol Infect Dis. 2022 May;103(1):115651. doi: 10.1016/j.diagmicrobio.2022.115651. Epub 2022 Jan 31.

Authors

Qingyu Zhang¹, Nicholas Neidig², Ting-Yu Chu³, Cameron Divoky⁴, Jessica Carpenter⁵, Cristian Lee-Hsiao⁶, Hillary Threatt⁶, Rasheda Sultana⁷, Karen Bush⁸

Affiliations

¹ Indiana University, Bloomington, IN, USA; Catalent Pharma Solutions, Bloomington, IN, USA; Research conducted at Indiana University, Bloomington, IN, USA.
² Indiana University, Bloomington, IN, USA; BioAgilytix, Durham, NC, USA; Research conducted at Indiana University, Bloomington, IN, USA.
³ Indiana University, Bloomington, IN, USA; Center for Discovery and Innovation, Nutley, NJ, USA; Research conducted at Indiana University, Bloomington, IN, USA.
⁴ Indiana University, Bloomington, IN, USA; The Ohio State University, Columbus, OH, USA; Research conducted at Indiana University, Bloomington, IN, USA.
⁵ Indiana University, Bloomington, IN, USA; Cook Medical, Bloomington, IN, USA; Research conducted at Indiana University, Bloomington, IN, USA.
⁶ Indiana University, Bloomington, IN, USA; Research conducted at Indiana University, Bloomington, IN, USA.
⁷ Indiana University, Bloomington, IN, USA; Sam Houston State University, Huntsville, TX, USA; Research conducted at Indiana University, Bloomington, IN, USA.
⁸ Indiana University, Bloomington, IN, USA; Research conducted at Indiana University, Bloomington, IN, USA. Electronic address: karbush@indiana.edu.

PMID: 35228130
DOI: 10.1016/j.diagmicrobio.2022.115651

Abstract

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.

Keywords: Carbapenemase; Cefiderocol; Enterobacterales; Siderophore.

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Azabicyclo Compounds
Carbapenems* / pharmacology
Cefiderocol
Cephalosporins* / pharmacology
Drug Combinations
Humans
Meropenem / pharmacology
Microbial Sensitivity Tests
beta-Lactamases / genetics

Substances

Anti-Bacterial Agents
Azabicyclo Compounds
Carbapenems
Cephalosporins
Drug Combinations
beta-Lactamases
Meropenem