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.

Department of Microbiology 3rd Faculty of Medicine Kralovske Vinohrady University Hospital and National Institute of Public Health Charles University Prague Czech Republic

National Reference Laboratory for Antibiotics Centre for Epidemiology and Microbiology National Institute of Public Health Prague Czech Republic

Zobrazit více v PubMed

Cassini A, Högberg LD, Plachouras D, et al. . Attributable deaths and disabilityadjusted life-years caused by infections with antibiotic resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis. Lancet Infect Dis 2019;19:56–66. PubMed PMC

Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States 2019. 2019. Available from: https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf [Last accessed: September 22, 2021].

Mushtaq S, Sadouki Z, Vickers A, et al. . In vitro activity of cefiderocol, a siderophore cephalosporin, against multidrug-resistant Gram-negative bacteria. Antimicrob Agents Chemother 2020;17:e01582-20. PubMed PMC

Iregui A, Khan Z, Landman D, Quale J. Activity of cefiderocol against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii endemic to medical centers in New York City. Microb Drug Resist 2020;26:722–726. PubMed PMC

Kohira N, West J, Ito A, et al. . In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother 2016;60:729–734. PubMed PMC

Hackel MA, Tsuji M, Yamano Y, et al. . In vitro activity of the siderophore cephalosporin, cefiderocol, against a recent collection of clinically relevant Gram-negative bacilli from North America and Europe, Including Carbapenem-Nonsusceptible Isolates (SIDERO-WT-2014 Stud). Antimicrob Agents Chemother 2017;61:e00093-17. PubMed PMC

Rahman MS, Koh YS. A novel antibiotic agent, cefiderocol, for multidrug-resistant Gram-negative bacteria. J Bacteriol Virol 2020;50:218–226.

Naseer S, Weinstein EA, Rubin DB, et al. . Benefit-Risk Considerations for Cefiderocol (Fetroja®). Clin Infect Dis 2021;72:e1103–e1111. PubMed

European Medicines Agency. Fetcroja (Cefiderocol) Summary of Product Characteristics. European Medicines Agency: Amsterdam, the Netherlands; 2020. Available from: https://www.ema.europa.eu/en/documents/product-information/fetcroja-epar-product-information_en.pdf [Last accessed: January 30, 2021].

Hrabák J, Walková R, Studentová V, et al. . Carbapenemase activity detection by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2011;49:3222–3227. PubMed PMC

EUCguideline for the detection of resistance mechanisms and specific resistances of clinical and AST/or epidemiological importance, v. 2.0. 2017. Available from: https://www.eucast.org/resistance_mechanisms [Last accessed: June 25, 2018].

Performance Standards for Antimicrobial Susceptibility Testing, 32nd Edition. Available from: https://clsi.org/standards [Last accessed: April 25, 2022].

Guidance document on broth microdilution testing of cefiderocol. 2020. Available from: https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Guidance_documents/Cefiderocol_MIC_testing_EUCAST_guidance_document_201217.pdf [Last accessed: January 18, 2021].

Wright H, Bonomo RA, Paterson DL. New agents for the treatment of infections with Gram-negative bacteria: Restoring the miracle or false dawn? Clin Microbiol Infect 2017;23:704–712. PubMed

Falagas ME, Skalidis T, Vardakas KZ, et al. . Activity of cefiderocol (S-649266) against carbapenem-resistant Gram-negative bacteria collected from inpatients in Greek hospitals. J Antimicrob Chemother 2017;72:1704–1708. PubMed

Rolston KVI, Gerges B, Shelburne S, et al. . Activity of cefiderocol and comparators against isolates from cancer patients. Antimicrob Agents Chemother 2020;64:e01955-19. PubMed PMC

Simner PJ, Beisken S, Bergman Y, et al. . Defining baseline mechanisms of cefiderocol resistance in the Enterobacterales. Microb Drug Resist 2022;28:161–170. PubMed PMC

Ong'uti S, Czech M, Robilotti E, Holubar M. Cefiderocol: A new cephalosporin stratagem against multidrug-resistant Gram-negative bacteria. Clin Infect Dis 2022;74:1303–1312. PubMed PMC

El-Lababidi RM, Rizk JG. Cefiderocol: A siderophore cephalosporin. Ann Pharmacother 2020;54:1215–1231. PubMed