{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T19:13:18Z","timestamp":1776885198055,"version":"3.51.2"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Pharmacy of the University of Coimbra and Center for Neurosciences and Cell Biology","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and Center for Neurosciences and Cell Biology","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and Center for Neurosciences and Cell Biology","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and Center for Neurosciences and Cell Biology","award":["UIDB\/AGR\/04033\/2020 321 (CITAB)"],"award-info":[{"award-number":["UIDB\/AGR\/04033\/2020 321 (CITAB)"]}]},{"name":"Faculty of Pharmacy of the University of Coimbra and Center for Neurosciences and Cell Biology","award":["UIDB\/CVT\/00772\/2020 (CEVAV)"],"award-info":[{"award-number":["UIDB\/CVT\/00772\/2020 (CEVAV)"]}]},{"name":"The research units Centre for the Research and Technology of Agro-Environmental and Biological Sciences","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"The research units Centre for the Research and Technology of Agro-Environmental and Biological Sciences","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"The research units Centre for the Research and Technology of Agro-Environmental and Biological Sciences","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"The research units Centre for the Research and Technology of Agro-Environmental and Biological Sciences","award":["UIDB\/AGR\/04033\/2020 321 (CITAB)"],"award-info":[{"award-number":["UIDB\/AGR\/04033\/2020 321 (CITAB)"]}]},{"name":"The research units Centre for the Research and Technology of Agro-Environmental and Biological Sciences","award":["UIDB\/CVT\/00772\/2020 (CEVAV)"],"award-info":[{"award-number":["UIDB\/CVT\/00772\/2020 (CEVAV)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Antimicrobial resistance continues to increase globally and treatment of difficult-to-treat (DTT) infections, mostly associated with carbapenem-resistant (CR) Pseudomonas aeruginosa, CR Acinetobacter baumannii, and CR- and third-generation-cephalosporins-resistant Enterobacterales remains a challenge for the clinician. The recent approval of cefiderocol has broaden the armamentarium for the treatment of patients with DTT infections. Cefiderocol is a siderophore cephalosporin that has shown excellent antibacterial activity, in part due to its innovative way of cell permeation. It is relatively stable compared to most commonly found carbapenamases. However, some resistant mechanisms to cefiderocol have already been identified and reduced susceptibility has developed during patient treatment, highlighting that the clinical use of cefiderocol must be rational. In this review, we summarize the current available treatments against the former resistant bacteria, and we revise and discuss the mechanism of action of cefiderocol, underlying the biological function of siderophores, the therapeutic potential of cefiderocol, and the mechanisms of resistance reported so far.<\/jats:p>","DOI":"10.3390\/life13071427","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T01:49:32Z","timestamp":1687398572000},"page":"1427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["An Overview of Cefiderocol\u2019s Therapeutic Potential and Underlying Resistance Mechanisms"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-5113","authenticated-orcid":false,"given":"Sara","family":"Domingues","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Tiago","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-4965","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Saavedra","sequence":"additional","affiliation":[{"name":"CITAB-Inov4Agro, Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CECAV-AL4AnimalS, Animal and Veterinary Research Center, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-8540","authenticated-orcid":false,"given":"Gabriela Jorge","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56033","DOI":"10.15252\/embr.202256033","article-title":"Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials","volume":"24","author":"Walesch","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_2","first-page":"268","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fpubh.2014.00145","article-title":"The antimicrobial resistance crisis: Causes, consequences, and management","volume":"2","author":"Michael","year":"2014","journal-title":"Front. Public Health"},{"key":"ref_4","first-page":"521","article-title":"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)","volume":"28","author":"Paul","year":"2022","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_5","unstructured":"(2023, April 05). Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Available online: https:\/\/wellcomecollection.org\/works\/rdpck35v."},{"key":"ref_6","unstructured":"World Health Organization (2017). Prioritization of Pathogens to Guide Discovery, Research and Development of New Antibiotics for Drug-Resistant Bacterial Infections, Including Tuberculosis, World Health Organization."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","unstructured":"World Health Organization (2021). 2020 Antibacterial Agents in Clinical and Preclinical Development: An Overview and Analysis, World Health Organization."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1093\/cid\/ciab1013","article-title":"Infectious Diseases Society of America guidance on the treatment of AmpC beta-lactamase-producing Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia infections","volume":"74","author":"Tamma","year":"2022","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/2049-632X.12125","article-title":"Acinetobacter baumannii: Evolution of a global pathogen","volume":"71","author":"Antunes","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1128\/JCM.36.7.1938-1941.1998","article-title":"Survival of Acinetobacter baumannii on dry surfaces: Comparison of outbreak and sporadic isolates","volume":"36","author":"Jawad","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1086\/504477","article-title":"Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa","volume":"43","author":"Bonomo","year":"2006","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Da Silva, G.J., and Domingues, S. (2016). Insights on the horizontal gene transfer of carbapenemase determinants in the opportunistic pathogen Acinetobacter baumannii. Microorganisms, 4.","DOI":"10.3390\/microorganisms4030029"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e006278","DOI":"10.1136\/bmjopen-2014-006278","article-title":"Seeking the source of Pseudomonas aeruginosa infections in a recently opened hospital: An observational study using whole-genome sequencing","volume":"4","author":"Quick","year":"2014","journal-title":"BMJ Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/cid\/ciac268","article-title":"Infectious Diseases Society of America 2022 guidance on the treatment of extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa)","volume":"75","author":"Tamma","year":"2022","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.1099\/ijsem.0.001485","article-title":"Genome-based phylogeny and taxonomy of the \u2018Enterobacteriales\u2019: Proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov","volume":"66","author":"Adeolu","year":"2016","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/s41564-018-0208-5","article-title":"A one-health approach to antimicrobial resistance","volume":"3","author":"Walsh","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fmicb.2019.00080","article-title":"Infections caused by carbapenem-resistant Enterobacteriaceae: An update on therapeutic options","volume":"10","author":"Sheu","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.synbio.2016.09.002","article-title":"Study on genetic engineering of Acremonium chrysogenum, the cephalosporin C producer","volume":"1","author":"Hu","year":"2016","journal-title":"Synth. Syst. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"617378","DOI":"10.3389\/fmed.2021.617378","article-title":"Novel cephalosporins in septic subjects and severe infections: Present findings and future perspective","volume":"8","author":"Corcione","year":"2021","journal-title":"Front. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40121-020-00395-2","article-title":"Continuous evolution: Perspective on the epidemiology of carbapenemase resistance among Enterobacterales and other Gram-negative bacteria","volume":"10","author":"Hansen","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_22","unstructured":"European Centre for Disease Prevention and Control, and World Health Organization (2023). Antimicrobial Resistance Surveillance in Europe 2023\u20132021 Data."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106528","DOI":"10.1016\/j.ijantimicag.2022.106528","article-title":"Carbapenemase-producing Enterobacterales infections: Recent advances in diagnosis and treatment","volume":"59","author":"Lee","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rodriguez-Bano, J., Gutierrez-Gutierrez, B., Machuca, I., and Pascual, A. (2018). Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clin. Microbiol. Rev., 31.","DOI":"10.1128\/CMR.00079-17"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4363","DOI":"10.2147\/IDR.S337611","article-title":"Emerging carbapenem-resistant Enterobacteriaceae infection, its epidemiology and novel treatment options: A review","volume":"14","author":"Tilahun","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1021\/acsinfecdis.5b00097","article-title":"Permeability barrier of Gram-negative cell envelopes and approaches to bypass it","volume":"1","author":"Zgurskaya","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1093\/jac\/dkaa217","article-title":"Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant Gram-negative bacilli","volume":"75","author":"Zhang","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.2174\/0929867323666160304150522","article-title":"Current advances in developing inhibitors of bacterial multidrug efflux pumps","volume":"23","author":"Mahmood","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.3389\/fmicb.2018.01301","article-title":"Identification of a novel polyamine scaffold with potent efflux pump inhibition activity toward multi-drug resistant bacterial pathogens","volume":"9","author":"Fleeman","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.chembiol.2015.03.018","article-title":"Toward the rational design of carbapenem uptake in Pseudomonas aeruginosa","volume":"22","author":"Isabella","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10534-009-9219-2","article-title":"Siderophores as drug delivery agents: Application of the \u201cTrojan Horse\u201d strategy","volume":"22","author":"Mollmann","year":"2009","journal-title":"Biometals Int. J. Role Met. Ions Biol. Biochem. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.chom.2013.04.010","article-title":"Iron in infection and immunity","volume":"13","author":"Cassat","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S529","DOI":"10.1093\/cid\/ciz825","article-title":"The role of iron and siderophores in infection, and the development of siderophore antibiotics","volume":"69","author":"Page","year":"2019","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41579-019-0284-4","article-title":"Bacterial siderophores in community and host interactions","volume":"18","author":"Kramer","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40121-020-00286-6","article-title":"Cefiderocol: A novel agent for the management of multidrug-resistant Gram-negative organisms","volume":"9","author":"Wu","year":"2020","journal-title":"Infect. Dis. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S538","DOI":"10.1093\/cid\/ciz826","article-title":"Cefiderocol: Discovery, chemistry, and in vivo profiles of a novel siderophore cephalosporin","volume":"69","author":"Sato","year":"2019","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1128\/AAC.03098-15","article-title":"Stability of novel siderophore cephalosporin S-649266 against clinically relevant carbapenemases","volume":"60","author":"Ishii","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e0007823","DOI":"10.1128\/aac.00078-23","article-title":"Impact of minor carbapenemases on susceptibility to novel beta-lactam\/beta-lactamase inhibitor combinations and cefiderocol in Enterobacterales","volume":"67","author":"Sadek","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","unstructured":"Food and Drug Administration (2019). NDA 209445: Cefiderocol."},{"key":"ref_40","unstructured":"European Medicines Agency (2020). Assessment Report-Fetcroja."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1007\/s40265-021-01580-4","article-title":"Cefiderocol: A review in serious Gram-negative bacterial infections","volume":"81","author":"Syed","year":"2021","journal-title":"Drugs"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S519","DOI":"10.1093\/cid\/ciz823","article-title":"Cefiderocol: A novel siderophore cephalosporin defeating carbapenem-resistant pathogens","volume":"69","author":"Bonomo","year":"2019","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s40265-019-1055-2","article-title":"Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant Gram-negative bacilli","volume":"79","author":"Zhanel","year":"2019","journal-title":"Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1473-3099(20)30731-3","article-title":"Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): A randomised, double-blind, phase 3, non-inferiority trial","volume":"21","author":"Wunderink","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S1473-3099(18)30554-1","article-title":"Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: A phase 2, randomised, double-blind, non-inferiority trial","volume":"18","author":"Portsmouth","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S1473-3099(20)30796-9","article-title":"Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): A randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial","volume":"21","author":"Bassetti","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mazzitelli, M., Gregori, D., Sasset, L., Trevenzoli, M., Scaglione, V., Lo Menzo, S., Marinello, S., Mengato, D., Venturini, F., and Tiberio, I. (2023). Cefiderocol-based versus colistin-based regimens for severe carbapenem-resistant Acinetobacter baumannii infections: A propensity score-weighted, retrospective cohort study during the first two years of the COVID-19 pandemic. Microorganisms, 11.","DOI":"10.3390\/microorganisms11040984"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"EVIDoa2200131","DOI":"10.1056\/EVIDoa2200131","article-title":"Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms","volume":"2","author":"Kaye","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e0267021","DOI":"10.1128\/spectrum.02670-21","article-title":"Occurrence of high levels of cefiderocol resistance in carbapenem-resistant Escherichia coli before its approval in China: A report from China CRE-network","volume":"10","author":"Wang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e0008422","DOI":"10.1128\/spectrum.00084-22","article-title":"Emergence of high-level cefiderocol resistance in carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in patients with hematologic malignancies in China","volume":"10","author":"Lan","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_51","unstructured":"European Committee on Antimicrobial Susceptibility Testing (2020). Clinical Breakpoints-Bacteria (v 10.0) (Jan 1, 2020)."},{"key":"ref_52","unstructured":"CLSI (2020). Performance Standards for Antimicrobial Susceptibility Testing, CLSI. [30th ed.]. CLSI Supplement M100."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e01025-20","DOI":"10.1128\/AAC.01025-20","article-title":"Achromobacter Infections and Treatment Options","volume":"64","author":"Isler","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Oueslati, S., Bogaerts, P., Dortet, L., Bernabeu, S., Ben Lakhal, H., Longshaw, C., Glupczynski, Y., and Naas, T. (2022). In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium. Antibiotics, 11.","DOI":"10.3390\/antibiotics11101352"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e01955-19","DOI":"10.1128\/AAC.01955-19","article-title":"Activity of Cefiderocol and Comparators against Isolates from Cancer Patients","volume":"64","author":"Rolston","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1754","DOI":"10.1093\/cid\/ciaa1847","article-title":"Cefiderocol for the Treatment of Adult and Pediatric Patients with Cystic Fibrosis and Achromobacter xylosoxidans Infections","volume":"73","author":"Warner","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Beauruelle, C., Lamoureux, C., Mashi, A., Ramel, S., Le Bihan, J., Ropars, T., Dirou, A., Banerjee, A., Tande, D., and Le Bars, H. (2021). In Vitro Activity of 22 Antibiotics against Achromobacter Isolates from People with Cystic Fibrosis. Are There New Therapeutic Options?. Microorganisms, 9.","DOI":"10.3390\/microorganisms9122473"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/jac\/dkab479","article-title":"Role of AxyABM overexpression in acquired resistance in Achromobacter xylosoxidans","volume":"77","author":"Magallon","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e00093-17","DOI":"10.1128\/AAC.00093-17","article-title":"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 Study)","volume":"61","author":"Hackel","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e0199021","DOI":"10.1128\/AAC.01990-21","article-title":"In Vitro Susceptibility of Gram-Negative Pathogens to Cefiderocol in Five Consecutive Annual Multinational SIDERO-WT Surveillance Studies, 2014 to 2019","volume":"66","author":"Karlowsky","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jgar.2021.12.017","article-title":"Characterisation of cefiderocol-non-susceptible Acinetobacter baumannii isolates from Taiwan","volume":"28","author":"Yamano","year":"2022","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e0087721","DOI":"10.1128\/AAC.00877-21","article-title":"Contribution of PER-type and NDM-type beta-lactamases to cefiderocol resistance in Acinetobacter baumannii","volume":"65","author":"Poirel","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e01221-20","DOI":"10.1128\/AAC.01221-20","article-title":"Cefiderocol resistance in Acinetobacter baumannii: Roles of beta-lactamases, siderophore receptors, and Penicillin Binding Protein 3","volume":"64","author":"Malik","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e01968-17","DOI":"10.1128\/AAC.01968-17","article-title":"In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Carbapenem-Nonsusceptible and Multidrug-Resistant Isolates of Gram-Negative Bacilli Collected Worldwide in 2014 to 2016","volume":"62","author":"Hackel","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ijantimicag.2018.11.007","article-title":"In Vitro Activity of Cefiderocol, a Siderophore Cephalosporin, Against Gram-Negative Bacilli Isolated by Clinical Laboratories in North America and Europe in 2015\u20132016: SIDERO-WT-2015","volume":"53","author":"Karlowsky","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1128\/AAC.01695-15","article-title":"In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains","volume":"60","author":"Kohira","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Alzahrani, O.M., Uddin, F., Mahmoud, S.F., Alswat, A.S., Sohail, M., and Youssef, M. (2022). Resistance to Some New Drugs and Prevalence of ESBL- and MBL-Producing Enterobacteriaceae Uropathogens Isolated from Diabetic Patients. Life, 12.","DOI":"10.3390\/life12122125"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e0031122","DOI":"10.1128\/aac.00311-22","article-title":"NDM-35-producing ST167 Escherichia coli highly resistant to beta-lactams including cefiderocol","volume":"66","author":"Poirel","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e0150522","DOI":"10.1128\/aac.01505-22","article-title":"Antimicrobial Activity of Cefiderocol against the Carbapenemase-Producing Enterobacter cloacae Complex and Characterization of Reduced Susceptibility Associated with Metallo-beta-Lactamase VIM-1","volume":"67","author":"Outeda","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e02011-21","DOI":"10.1128\/aac.02011-21","article-title":"New Delhi metallo-beta-lactamase facilitates the emergence of cefiderocol resistance in Enterobacter cloacae","volume":"66","author":"Nurjadi","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"dlab081","DOI":"10.1093\/jacamr\/dlab081","article-title":"In vitro activity of cefiderocol and comparators against isolates of Gram-negative pathogens from a range of infection sources: SIDERO-WT-2014-2018 studies in France","volume":"3","author":"Naas","year":"2021","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.jgar.2021.04.019","article-title":"In vitro activity of cefiderocol and comparators against isolates of Gram-negative pathogens from a range of infection sources: SIDERO-WT-2014-2018 studies in Italy","volume":"25","author":"Stracquadanio","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_73","first-page":"001406","article-title":"Pan-drug resistant Providencia rettgeri contributing to a fatal case of COVID-19","volume":"70","author":"Geringer","year":"2021","journal-title":"J. Med. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Padovani, M., Bertelli, A., Corbellini, S., Piccinelli, G., Gurrieri, F., and De Francesco, M.A. (2023). In vitro activity of cefiderocol on multiresistant bacterial strains and genomic analysis of two cefiderocol resistant strains. Antibiotics, 12.","DOI":"10.3390\/antibiotics12040785"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e4472","DOI":"10.1093\/cid\/ciaa1909","article-title":"Evolution of Cefiderocol Non-Susceptibility in Pseudomonas aeruginosa in a Patient without Previous Exposure to the Antibiotic","volume":"73","author":"Streling","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10096-022-04526-0","article-title":"Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa","volume":"42","author":"Sadek","year":"2023","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"dlac011","DOI":"10.1093\/jacamr\/dlac011","article-title":"Evolution of cefiderocol resistance in Stenotrophomonas maltophilia using in vitro serial passage techniques","volume":"4","author":"Werth","year":"2022","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e01454-17","DOI":"10.1128\/AAC.01454-17","article-title":"In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against Gram-negative bacteria","volume":"62","author":"Ito","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10096-021-04397-x","article-title":"Co-resistance to ceftazidime-avibactam and cefiderocol in clinical isolates producing KPC variants","volume":"41","author":"Poirel","year":"2022","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e0003922","DOI":"10.1128\/aac.00039-22","article-title":"Impact of acquired broad-spectrum beta-lactamases on susceptibility to cefiderocol and newly developed beta-lactam\/beta-lactamase inhibitor combinations in Escherichia coli and Pseudomonas aeruginosa","volume":"66","author":"Poirel","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_81","first-page":"2200795","article-title":"Nosocomial outbreak by NDM-1-producing Klebsiella pneumoniae highly resistant to cefiderocol, Florence, Italy, August 2021 to June 2022","volume":"27","author":"Coppi","year":"2022","journal-title":"Euro Surveill. Bull. Eur. Sur Les Mal. Transm. Eur. Commun. Dis. Bull."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e0264620","DOI":"10.1128\/AAC.02646-20","article-title":"In vitro antibacterial activity of cefiderocol against multidrug-resistant Acinetobacter baumannii","volume":"65","author":"Nguyen","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","first-page":"1172.e7","article-title":"Cross-resistance to cefiderocol and ceftazidime-avibactam in KPC beta-lactamase mutants and the inoculum effect","volume":"27","author":"Hobson","year":"2021","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1093\/cid\/ciaa355","article-title":"Clinical evolution of AmpC-mediated ceftazidime-avibactam and cefiderocol resistance in Enterobacter cloacae complex following exposure to cefepime","volume":"71","author":"Shields","year":"2020","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e00198-20","DOI":"10.1128\/AAC.00198-20","article-title":"Structural basis of reduced susceptibility to ceftazidime-avibactam and cefiderocol in Enterobacter cloacae due to AmpC R2 loop deletion","volume":"64","author":"Kawai","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"dlaa081","DOI":"10.1093\/jacamr\/dlaa081","article-title":"Escherichia coli strains possessing a four amino acid YRIN insertion in PBP3 identified as part of the SIDERO-WT-2014 surveillance study","volume":"2","author":"Sato","year":"2020","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1089\/mdr.2021.0180","article-title":"Mechanisms of reduced susceptibility to cefiderocol among isolates from the CREDIBLE-CR and APEKS-NP clinical trials","volume":"28","author":"Nordmann","year":"2022","journal-title":"Microb. Drug Resist."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"S649","DOI":"10.1093\/ofid\/ofaa439.1450","article-title":"1266. Characterization of shifts in minimum inhibitory concentrations during treatment with cefiderocol or comparators in the phase 3 CREDIBLE-CR and APEKS-NP studies","volume":"7","author":"Takemura","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e0011823","DOI":"10.1128\/aac.00118-23","article-title":"Genomic modification of TonB andeEmergence of small-colony phenotype in VIM- and NDM-producing Escherichia coli following cefiderocol exposure in vitro","volume":"67","author":"Kocer","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/cid\/ciab511","article-title":"Rapid development of cefiderocol resistance in carbapenem-resistant Enterobacter cloacae during therapy is associated with heterogeneous mutations in the catecholate siderophore receptor cirA","volume":"74","author":"Klein","year":"2022","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/ajcp\/aqab115","article-title":"Case report and genomic analysis of cefiderocol-resistant Escherichia coli clinical isolates","volume":"157","author":"Price","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e0017123","DOI":"10.1128\/aac.00171-23","article-title":"Exploring cefiderocol resistance mechanisms in Burkholderia pseudomallei","volume":"67","author":"Hall","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e0177921","DOI":"10.1128\/Spectrum.01779-21","article-title":"In vitro evolution of cefiderocol resistance in an NDM-producing Klebsiella pneumoniae due to functional loss of CirA","volume":"9","author":"McElheny","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1093\/jac\/dkac022","article-title":"Relationship of TonB-dependent receptors with susceptibility to cefiderocol in clinical isolates of Pseudomonas aeruginosa","volume":"77","author":"Gupta","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/cid\/ciab888","article-title":"Progressive development of cefiderocol resistance in Escherichia coli during therapy is associated with an increase in blaNDM-5 copy number and gene expression","volume":"75","author":"Simner","year":"2022","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e1261","DOI":"10.1093\/cid\/ciac647","article-title":"Evolution and Transmission of Cefiderocol-Resistant Acinetobacter baumannii During an Outbreak in the Burn Intensive Care Unit","volume":"76","author":"Smoke","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Sansone, P., Giaccari, L.G., Coppolino, F., Aurilio, C., Barbarisi, A., Passavanti, M.B., Pota, V., and Pace, M.C. (2022). Cefiderocol for carbapenem-resistant bacteria: Handle with care! A review of the real-world evidence. Antibiotics, 11.","DOI":"10.3390\/antibiotics11070904"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1089\/mdr.2021.0095","article-title":"Defining baseline mechanisms of cefiderocol resistance in the Enterobacterales","volume":"28","author":"Simner","year":"2022","journal-title":"Microb. Drug Resist."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7177","DOI":"10.2147\/IDR.S392241","article-title":"Resistance to cefiderocol involved expression of PER-1 beta-lactamase and downregulation of iron transporter system in carbapenem-resistant Acinetobacter baumannii","volume":"15","author":"He","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S1473-3099(21)00194-8","article-title":"Widespread cefiderocol heteroresistance in carbapenem-resistant Gram-negative pathogens","volume":"21","author":"Choby","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e648","DOI":"10.1016\/S2666-5247(21)00271-8","article-title":"Does cefiderocol heteroresistance explain the discrepancy between the APEKS-NP and CREDIBLE-CR clinical trial results?","volume":"2","author":"Choby","year":"2021","journal-title":"Lancet Microbe"},{"key":"ref_102","unstructured":"European Committee on Antimicrobial Susceptibility Testing (2020). Guidance Document on Broth Microdilution Testing of Cefiderocol, European Committee on Antimicrobial Susceptibility Testing."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/7\/1427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:58:24Z","timestamp":1760126304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/7\/1427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":102,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["life13071427"],"URL":"https:\/\/doi.org\/10.3390\/life13071427","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}