{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:54:29Z","timestamp":1781765669105,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Cefiderocol (FDC) is a siderophore-containing cephalosporin that retains activity against many \u03b2-lactamase-producing bacteria, such as New Delhi metallo-\u03b2-latamase-producing (NDM) K. pneumoniae. Its use in critically ill patients is still limited, since the recommended dosing regimens are mainly derived from studies on healthy subjects, while critical illness is often associated with critical alterations in drug pharmacokinetics. Therefore, the aim of this study was to investigate FDC pharmacokinetic\/pharmacodynamic (PK\/PD) parameters in real-life patients based on their body weight and renal function. Methods: Patients with K. pneumoniae infections and indications for FDC were enrolled. Drug quantification in plasma was performed at the steady state at different timings. PK\/PD targets of fCmin &gt; 4 mg\/L (most common) and more stringent targets of fCmin &gt; 8 and 12 mg\/L (4\u00d7 and 6\u00d7 the EUCAST breakpoint MIC) were considered in relation to patients\u2019 characteristics, 14 days of microbiological eradication and 30-day mortality. Results: Ten patients were enrolled in this study. Mortality, as well as the failure to achieve microbiological eradication, increased with BMI. In a PK\/PD point of view, all patients reached the PK\/PD targets of fCmin &gt; 4 mg\/L and &gt; 8 mg\/L, while only 20% reached a fCmin &gt; 12 mg\/L, with a key influence of renal function. However, no significant association was found between PK\/PD target attainment and treatment outcomes. Conclusions: Our study may be useful for the real-world use of FDC, highlighting the impact of renal function on the achievement of ideal PK\/PD thresholds. Nevertheless, the lack of a significant association between PK\/PD and outcomes, partially due to the small sample size, highlights the complex impact of patients\u2019 clinical conditions other than drug PK.<\/jats:p>","DOI":"10.3390\/antibiotics15060619","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:52:37Z","timestamp":1781761957000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Evidence: Cefiderocol Therapeutic Drug Monitoring in Critically Ill, Obese Patients with Klebsiella pneumoniae Infections"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-6709","authenticated-orcid":false,"given":"Alessandra","family":"Manca","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0860-280X","authenticated-orcid":false,"given":"Alice","family":"Palermiti","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Corcione","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Infectious Disease, University of Turin, City of Health and Science Hospital, 10126 Turin, Italy"},{"name":"Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8253-4351","authenticated-orcid":false,"given":"Giorgia","family":"Menegatti","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-9694","authenticated-orcid":false,"given":"Jessica","family":"Cusato","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Grosso","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Infectious Disease, University of Turin, City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Risso","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-965X","authenticated-orcid":false,"given":"Giorgia Giuseppina","family":"Montrucchio","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, University of Turin, 10124 Turin, Italy"},{"name":"Department of Anesthesia, Intensive Care and Emergency, City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Scabini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Infectious Diseases, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-2141","authenticated-orcid":false,"given":"Filippo","family":"Mariano","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation U, Department of Medical Sciences, University of Turin, City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-9948","authenticated-orcid":false,"given":"Amedeo","family":"De Nicol\u00f2","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8338-0130","authenticated-orcid":false,"given":"Francesco Giuseppe","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Infectious Diseases, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1321-4126","authenticated-orcid":false,"given":"Antonio","family":"D\u2019Avolio","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s40121-025-01147-w","article-title":"From Clinical Trials to Real-World Experiences: Evidence About Cefiderocol Use and Potential Role in Empirical Therapy","volume":"14","author":"Russo","year":"2025","journal-title":"Infect. Dis. Ther."},{"key":"ref_2","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_3","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_4","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_5","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International Study of the Prevalence and Outcomes of Infection in Intensive Care Units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1086\/499406","article-title":"The Relationship between Antimicrobial Resistance and Patient Outcomes: Mortality, Length of Hospital Stay, and Health Care Costs","volume":"42","author":"Cosgrove","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shiozawa, M., Kaneko, H., Itoh, H., Morita, K., Okada, A., Matsuoka, S., Kiriyama, H., Kamon, T., Fujiu, K., and Michihata, N. (2021). Association of Body Mass Index with Ischemic and Hemorrhagic Stroke. Nutrients, 13.","DOI":"10.3390\/nu13072343"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40560-023-00660-9","article-title":"Onset Timing and Duration of Augmented Renal Clearance in a Mixed Intensive Care Unit","volume":"11","author":"Mikami","year":"2023","journal-title":"J. Intensive Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/17512433.2021.1901574","article-title":"Pharmacokinetic\/Pharmacodynamic Target Attainment in Critically Ill Renal Patients on Antimicrobial Usage: Focus on Novel Beta-Lactams and Beta Lactams\/Beta-Lactamase Inhibitors","volume":"14","author":"Gatti","year":"2021","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gorham, J., Taccone, F.S., and Hites, M. (2022). Drug Regimens of Novel Antibiotics in Critically Ill Patients with Varying Renal Functions: A Rapid Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11050546"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"ofab252","DOI":"10.1093\/ofid\/ofab252","article-title":"Cefiderocol Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemodiafiltration","volume":"8","author":"Kobic","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S651","DOI":"10.1093\/ofid\/ofaa439.1453","article-title":"1269. Differences in Interpretative Breakpoints Between CLSI, FDA and EUCAST Impact Reporting of Susceptibility and Resistance to Cefiderocol","volume":"7","author":"Yamano","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"K\u00f6nig, C., Both, A., Rohde, H., Kluge, S., Frey, O.R., R\u00f6hr, A.C., and Wichmann, D. (2021). Cefiderocol in Critically Ill Patients with Multi-Drug-Resistant Pathogens: Real-Life Data on Pharmacokinetics and Microbiological Surveillance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10060649"},{"key":"ref_14","unstructured":"U.S. Food and Drug Administration (2025). FDA Rationale for Recognition Decision: Cefiderocol."},{"key":"ref_15","unstructured":"(2026, April 28). V_16.0_Breakpoint_Tables.Pdf. Available online: https:\/\/www.eucast.org\/fileadmin\/eucast\/pdf\/breakpoints\/v_16.0_Breakpoint_Tables.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gatti, M., and Pea, F. (2026). Raising the Bar of PK\/PD Target Attainment of Beta-Lactams in Daily Clinical Practice: An Effective Strategy to Overcome Resistance Development to Novel Beta-Lactams?. Infect. Dis. Rep., 18.","DOI":"10.3390\/idr18010003"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13054-024-04911-5","article-title":"Impact of Attaining Aggressive vs. Conservative PK\/PD Target on the Clinical Efficacy of Beta-Lactams for the Treatment of Gram-Negative Infections in the Critically Ill Patients: A Systematic Review and Meta-Analysis","volume":"28","author":"Gatti","year":"2024","journal-title":"Crit. Care"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bakdach, D., Elajez, R., Bakdach, A.R., Awaisu, A., De Pascale, G., and Ait Hssain, A. (2022). Pharmacokinetics, Pharmacodynamics, and Dosing Considerations of Novel \u03b2-Lactams and \u03b2-Lactam\/\u03b2-Lactamase Inhibitors in Critically Ill Adult Patients: Focus on Obesity, Augmented Renal Clearance, Renal Replacement Therapies, and Extracorporeal Membrane Oxygenation. J. Clin. Med., 11.","DOI":"10.3390\/jcm11236898"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106395","DOI":"10.1016\/j.ijantimicag.2021.106395","article-title":"Optimised Cefiderocol Exposures in a Successfully Treated Critically Ill Patient with Polymicrobial Stenotrophomonas Maltophilia Bacteraemia and Pneumonia Receiving Continuous Venovenous Haemodiafiltration","volume":"58","author":"Fratoni","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_20","unstructured":"AIFA (2026, June 10). Fetcroja, INN-Cefiderocol, Available online: https:\/\/api.aifa.gov.it\/aifa-bdf-eif-be\/1.0.0\/organizzazione\/5017\/farmaci\/48722\/stampati?ts=RCP."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"ofae451","DOI":"10.1093\/ofid\/ofae451","article-title":"Validation of Cefiderocol Package Insert Dosing Recommendation for Patients Receiving Continuous Renal Replacement Therapy: A Prospective Multicenter Pharmacokinetic Study","volume":"11","author":"Fouad","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/ndt\/gfp392","article-title":"Comparison of Methods for Estimating Glomerular Filtration Rate in Critically Ill Patients with Acute Kidney Injury","volume":"25","author":"Bouchard","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mornese Pinna, S., Corcione, S., De Nicol\u00f2, A., Montrucchio, G., Scabini, S., Vita, D., De Benedetto, I., Lupia, T., Mula, J., and Di Perri, G. (2022). Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121830"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114790","DOI":"10.1016\/j.biopha.2023.114790","article-title":"Analytical Validation of a Novel UHPLC-MS\/MS Method for 19 Antibiotics Quantification in Plasma: Implementation in a LC-MS\/MS Kit","volume":"163","author":"Mula","year":"2023","journal-title":"Biomed. Pharmacother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/6\/619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:16:54Z","timestamp":1781763414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/6\/619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["antibiotics15060619"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15060619","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]}}}