{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:49Z","timestamp":1785427309195,"version":"3.56.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201600029C"],"award-info":[{"award-number":["HHSN272201600029C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Ledaborbactam etzadroxil (LED-E) is an oral prodrug of ledaborbactam, a broad-spectrum \u03b2-lactamase inhibitor. In combination with ceftibuten (CTB), a third-generation oral cephalosporin, LED-E represents a potential oral \u03b2-lactam\/\u03b2-lactamase inhibitor regimen for treating infections caused by drug-resistant Gram-negative pathogens. This phase 1, single-center, open-label study evaluated intrapulmonary concentrations of ledaborbactam (LED) and CTB in healthy adults. Participants in Group 1 received five oral doses of CTB\/LED-E (600 mg\/600 mg) every 12 h (q12h), and participants in Group 2 received five oral doses of CTB 600 mg q12h. Following the fifth dose, participants underwent a standardized single bronchoscopy with bronchoalveolar lavage (BAL). Twenty-eight participants in Group 1 and six participants in Group 2 were randomized and dosed. Among participants receiving CTB\/LED-E, epithelial lining fluid (ELF) area under the concentration-time curve from 0 to 12 h (AUC\n                      <jats:sub>0\u201312<\/jats:sub>\n                      ) for aspirate 1 was 14,867 ng\u00b7h\/mL for CTB and 14,529 ng\u00b7h\/mL for LED, and for pooled aspirates 2 + 3 + 4 was 10,486 ng\u00b7h\/mL and 9,809 ng\u00b7h\/mL, respectively. ELF-to-unbound plasma AUC ratios were 0.341 (aspirate 1) and 0.239 (pooled aspirates 2 + 3 + 4) for CTB and 1.560 and 1.032, respectively, for LED. Participants receiving CTB alone demonstrated similar lung penetration, indicating no effect of LED on CTB exposure. Both CTB\/LED-E and CTB alone were safe and well tolerated; all adverse events were mild or moderate and unrelated to study drug. These results demonstrate pulmonary penetration of CTB and LED and support further evaluation of CTB\/LED-E for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.\n                    <\/jats:p>\n                    <jats:p>\n                      This study is registered with ClinicalTrials.gov as\n                      <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT06665555\" document-id-type=\"clinical-trial-number\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06665555\">NCT06665555<\/jats:related-object>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01950-25","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:30:45Z","timestamp":1776709845000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Plasma and intrapulmonary pharmacokinetics of ceftibuten and ledaborbactam in healthy male and female adults"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-7346","authenticated-orcid":true,"given":"Keith A.","family":"Rodvold","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02mpq6x41","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Illinois Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Gotfried","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048qnxy85","id-type":"ROR","asserted-by":"publisher"}],"name":"Pulmonary Associates, PA","place":["Phoenix, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4989-4896","authenticated-orcid":true,"given":"Carlos Fernando","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Lowe","sequence":"additional","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-9736","authenticated-orcid":true,"given":"Kamal A.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8243-0482","authenticated-orcid":true,"given":"Karine","family":"Litherland","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-0212","authenticated-orcid":true,"given":"Marc","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd","place":["Allschwil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-2818","authenticated-orcid":false,"given":"Paul C.","family":"McGovern","sequence":"additional","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_3_3_2","volume-title":"WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance","author":"WHO","year":"2024","unstructured":"WHO. 2024. 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Cedax (ceftibuten capsules and ceftibuten for oral suspension). Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/050686s016lbl.pdf. Retrieved 16 Dec 2025."},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg355"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.8.2450-2457.2003"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1399"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.60.2.532"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01950-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01950-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:02:52Z","timestamp":1781787772000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01950-25"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,3]]}},"alternative-id":["10.1128\/aac.01950-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01950-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2025-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01950-25"}}