Rapid communication Open Access
Like 0


A nosocomial outbreak by cefiderocol (FDC)-resistant NDM-1-producing (NDM-Kp) occurred in a large tertiary care hospital from August 2021–June 2022 in Florence, Italy, an area where NDM-Kp strains have become endemic. Retrospective analysis of NDM-Kp from cases observed in January 2021–June 2022 revealed that 21/52 were FDC-resistant. The outbreak was mostly sustained by clonal expansion of a mutant with inactivated siderophore receptor gene, which exhibited high-level resistance to FDC (MIC ≥ 32 mg/L) and spread independently of FDC exposure.


Article metrics loading...

Loading full text...

Full text loading...



  1. Bassetti M, Di Pilato V, Giani T, Vena A, Rossolini GM, Marchese A, et al. Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria. Future Microbiol. 2020;15(15):1489-505.  https://doi.org/10.2217/fmb-2020-0210  PMID: 33140656 
  2. Paul M, Carrara E, Retamar P, Tängdén T, Bitterman R, Bonomo RA, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clin Microbiol Infect. 2022;28(4):521-47.  https://doi.org/10.1016/j.cmi.2021.11.025  PMID: 34923128 
  3. Gaibani P, Giani T, Bovo F, Lombardo D, Amadesi S, Lazzarotto T, et al. Resistance to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam in Gram-Negative MDR bacilli: molecular mechanisms and susceptibility testing. Antibiotics (Basel). 2022;11(5):628.  https://doi.org/10.3390/antibiotics11050628  PMID: 35625273 
  4. Lan P, Lu Y, Chen Z, Wu X, Hua X, Jiang Y, et al. Emergence of high-level cefiderocol resistance in carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in patients with hematologic malignancies in China. Microbiol Spectr. 2022;10(2):e0008422.  https://doi.org/10.1128/spectrum.00084-22  PMID: 35323031 
  5. Klein S, Boutin S, Kocer K, Fiedler MO, Störzinger D, Weigand MA, et al. Rapid development of cefiderocol resistance in carbapenem-resistant Enterobacter cloacae during therapy is associated with heterogeneous mutations in the catecholate siderophore receptor cirA. Clin Infect Dis. 2022;74(5):905-8.  https://doi.org/10.1093/cid/ciab511  PMID: 34079986 
  6. Karakonstantis S, Rousaki M, Kritsotakis EI. Cefiderocol: systematic review of mechanisms of resistance, heteroresistance and in vivo emergence of resistance. Antibiotics (Basel). 2022;11(6):723.  https://doi.org/10.3390/antibiotics11060723  PMID: 35740130 
  7. Falcone M, Tiseo G, Antonelli A, Giordano C, Di Pilato V, Bertolucci P, et al. Clinical features and outcomes of bloodstream infections caused by New Delhi metallo-β-lactamase–producing Enterobacterales during a regional outbreak. Open Forum Infect Dis. 2020;7(2):ofaa011.  https://doi.org/10.1093/ofid/ofaa011  PMID: 32042848 
  8. Tavoschi L, Forni S, Porretta A, Righi L, Pieralli F, Menichetti F, et al. , Tuscan Clinical Microbiology Laboratory Network. Prolonged outbreak of New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019. Euro Surveill. 2020;25(6).  https://doi.org/10.2807/1560-7917.ES.2020.25.6.2000085  PMID: 32070467 
  9. Di Pilato V, Henrici De Angelis L, Aiezza N, Baccani I, Niccolai C, Parisio EM, et al. , Tuscan Clinical Microbiology Laboratory Network. Resistome and virulome accretion in an NDM-1-producing ST147 sublineage of Klebsiella pneumoniae associated with an outbreak in Tuscany, Italy: a genotypic and phenotypic characterisation. Lancet Microbe. 2022;3(3):e224-34.  https://doi.org/10.1016/S2666-5247(21)00268-8  PMID: 35544076 
  10. Simner PJ, Patel R. Cefiderocol antimicrobial susceptibility testing considerations: the Achilles’ heel of the Trojan horse? J Clin Microbiol. 2020;59(1):e00951-20.  https://doi.org/10.1128/JCM.00951-20  PMID: 32727829 
  11. Morris CP, Bergman Y, Tekle T, Fissel JA, Tamma PD, Simner PJ. Cefiderocol antimicrobial susceptibility testing against multidrug-resistant Gram-Negative bacilli: a comparison of disk diffusion to broth microdilution. J Clin Microbiol. 2020;59(1):e01649-20.  https://doi.org/10.1128/JCM.01649-20  PMID: 32938734 
  12. European Committee on Antimicrobial Susceptibility Testing (EUCAST). EUCAST warnings concerning antimicrobial susceptibility testing products or procedures. Växjö: EUCAST. [Accessed: 20 Jun 2022]. Available from: https://www.eucast.org/ast_of_bacteria/warnings
  13. Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. Reproducibility of broth microdilution MICs for the novel siderophore cephalosporin, cefiderocol, determined using iron-depleted cation-adjusted Mueller-Hinton broth. Diagn Microbiol Infect Dis. 2019;94(4):321-5.  https://doi.org/10.1016/j.diagmicrobio.2019.03.003  PMID: 31029489 
  14. Simner PJ, Beisken S, Bergman Y, Ante M, Posch AE, Tamma PD. Defining baseline mechanisms of cefiderocol resistance in the Enterobacterales. Microb Drug Resist. 2022;28(2):161-70.  https://doi.org/10.1089/mdr.2021.0095  PMID: 34619049 
  15. International Organization for Standardization (ISO). Clinical laboratory testing and in vitro diagnostic test systems. Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices—part 1: reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. ISO20776-1:2019. Available from: https://www.iso.org/standard/70464.html
  16. The European Committee on Antimicrobial Susceptibility Testing (EUCAST). Clinical breakpoints - breakpoints and guidance (v.12). Växjö: EUCAST; 1 Jan 2020. Available from: https://eucast.org/clinical_breakpoints
  17. Matuschek E, Longshaw C, Takemura M, Yamano Y, Kahlmeter G. Cefiderocol: EUCAST criteria for disc diffusion and broth microdilution for antimicrobial susceptibility testing. J Antimicrob Chemother. 2022;77(6):1662-9.  https://doi.org/10.1093/jac/dkac080  PMID: 35289853 
  18. McElheny CL, Fowler EL, Iovleva A, Shields RK, Doi Y. In vitro evolution of cefiderocol resistance in an NDM-producing Klebsiella pneumoniae due to functional loss of CirA. Microbiol Spectr. 2021;9(3):e0177921.  https://doi.org/10.1128/Spectrum.01779-21  PMID: 34756080 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error