{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:28:02Z","timestamp":1753882082997,"version":"3.41.2"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100005612","name":"Shionogi","doi-asserted-by":"crossref","award":["Investigator Initiated Grant"],"award-info":[{"award-number":["Investigator Initiated Grant"]}],"id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Persons with CF (pwCF) present altered pharmacokinetics (PK) and are often infected with multidrug-resistant (MDR) bacteria. Herein, we describe the PK of cefiderocol, a siderophore cephalosporin with potent activity against MDR Gram-negative rods, in hospitalized adult pwCF with acute pulmonary exacerbation (APE). PwCF received \u22653 doses of 2 g cefiderocol (3 h infusion) with frequency determined according to their estimated glomerular filtration rate (eGFR). Blood sampling collected at steady state. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. Ten pwCF were enrolled; nine completed the study with six receiving 2 g q8 h and three 2 g q6 h. A two-compartment model best fitted the data. Mean (SD) PK parameters were clearance, 5.66 (1.28) L\/h; volume of central compartment, 5.81 (3.52) L, and intercompartment transfer constants, k12, 4.29 (3.46) and k21, 2.25 (2.76) h\n              <jats:sup>\u22121<\/jats:sup>\n              . Protein binding was 48% (35\u201357). The 2 g q8 h regimen achieved a mean free time above the MIC (\n              <jats:italic>f<\/jats:italic>\n              T &gt;MIC) of 99% (94\u201399), 90% (69\u2013100), and 64% (41\u201381) at MICs of 4 (susceptible), 8 (intermediate), and 16 (resistant) mg\/L, respectively, with AUC\n              <jats:sub>24h<\/jats:sub>\n              of 1,191 (781\u20131,496) mg\/L*h. In pwCF with eGFR &gt;120 mL\/min, 2 g q6 h attained 100%\n              <jats:italic>f<\/jats:italic>\n              T &gt;MIC up to 8 mg\/L and 87% (83\u201392) at 16 mg\/L, with AUC\n              <jats:sub>24h<\/jats:sub>\n              of 1,279 (1,054\u20131,590) mg\/L*h. Among these nine pwCF with APE with normal or augmented renal clearance, cefiderocol using label prescribed dosing regimens according to eGFR was well tolerated and achieved optimal\n              <jats:italic>f<\/jats:italic>\n              T &gt;MIC exposure for pathogens up to MICs of 8 mg\/L and AUC\n              <jats:sub>24h<\/jats:sub>\n              estimates similar to previously reported estimates in non-CF patients.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01539-24","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T14:01:15Z","timestamp":1733839275000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Cefiderocol pharmacokinetics during acute pulmonary exacerbations in hospitalized adult persons with cystic fibrosis"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-3496","authenticated-orcid":false,"given":"Christina","family":"Koenig","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research & Development, Hartford Hospital","place":["Hartford, USA"]},{"name":"Intensive Care Medicine, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-458X","authenticated-orcid":true,"given":"Marguerite L.","family":"Monogue","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-5665","authenticated-orcid":true,"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center","place":["Pittsburgh, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen M.","family":"Sakon","sequence":"additional","affiliation":[{"name":"Indiana University Health","place":["Indianapolis, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Fratoni","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research & Development, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna F.","family":"Roenfanz","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research & Development, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Finklea","sequence":"additional","affiliation":[{"name":"The University of Texas Southwestern Medical Center","place":["Dallas, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S.","family":"Pope","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4148-0165","authenticated-orcid":true,"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research & Development, Hartford Hospital","place":["Hartford, USA"]},{"name":"Division of Infectious Diseases, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-3126","authenticated-orcid":true,"given":"Joseph L.","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research & Development, Hartford Hospital","place":["Hartford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2216474"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110052"},{"key":"e_1_3_5_4_2","unstructured":"Foundation CF. 2023. Patient registry annual data report 2022."},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201404-166OC"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae391"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812-1845PP"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30796-9"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-024-00709-z"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2024.01.023"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01566-16"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0306-9877(98)90070-6"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.1836157"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198815010-00005"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1984.187"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt300"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv289"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199835040-00004"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11060286"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101436"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0678-x"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01437-20"},{"key":"e_1_3_5_23_2","unstructured":"Food and Drug Administration. 2020. Fetroja (Cefiderocol) product information. 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CLSI M100 performance standards for antimicrobial susceptibility testing. 34th ed. 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