{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:45:33Z","timestamp":1790646333793,"version":"4.1.0"},"reference-count":12,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201600029C"],"award-info":[{"award-number":["HHSN272201600029C"]}],"id":[{"id":"10.13039\/100000060","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":[[2025,9,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Ledaborbactam etzadroxil, the prodrug of the active \u03b2-lactamase inhibitor ledaborbactam, is being developed in combination with ceftibuten to treat serious infections caused by drug-resistant Enterobacterales. This study evaluated the safety and pharmacokinetics of ceftibuten in healthy adults at anticipated higher doses required, in combination with ledaborbactam etzadroxil, to treat Enterobacterales infections. Thirty-six participants (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 12 per cohort [ceftibuten\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 9, placebo\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 3]) received a single oral dose of ceftibuten (400, 800, or 1,200 mg) or matched placebo on day 1. Following a one-day washout, the same participants received repeat oral doses of ceftibuten (400 mg once daily, 400 mg every 12 hours [q12h], or 400 mg q8h) for 10 days. Of the 36 participants, 25 (ceftibuten 67%, placebo 78%) reported 65 treatment-emergent adverse events (TEAEs). Nausea (22%), headache (15%), and fatigue (15%) were the most reported TEAEs among ceftibuten-treated participants. No participant experienced serious adverse events or discontinuations due to TEAEs. In both single- and multiple-dose cohorts, cis-ceftibuten isomer exposure was dose-proportional for areas under the curve (AUCs) but less than dose-proportional for maximum concentrations (\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ). Low levels of cis-ceftibuten accumulation were observed at steady state, with accumulation ratios of 1.06, 1.09, and 1.24 for the 400 mg once daily, q12h, and q8h cohorts, respectively. Cis-ceftibuten and trans-ceftibuten recovery in urine was 47% and 6%, respectively, following a single dose of 1,200 mg.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>CLINICAL TRIALS<\/jats:title>\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=\"NCT04314206\" 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\/NCT04314206\">NCT04314206<\/jats:related-object>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00087-25","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T20:15:28Z","timestamp":1755202528000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics and safety of single and repeat doses of ceftibuten in healthy participants: a phase 1 dose escalation study"],"prefix":"10.1128","volume":"69","author":[{"given":"Mary Beth","family":"Dorr","sequence":"first","affiliation":[{"name":"VenatoRx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4989-4896","authenticated-orcid":false,"given":"Carlos Fernando","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"VenatoRx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"van de Wetering","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02k5t6c64","id-type":"ROR","asserted-by":"publisher"}],"name":"PRA Health Sciences","place":["Groningen, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Lowe","sequence":"additional","affiliation":[{"name":"VenatoRx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Sabato","sequence":"additional","affiliation":[{"name":"VenatoRx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Winchell","sequence":"additional","affiliation":[{"name":"Winchell Pharma Consulting, LLC","place":["Norristown, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzi","family":"Chen","sequence":"additional","affiliation":[{"name":"VenatoRx Pharmaceuticals Inc","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-2818","authenticated-orcid":true,"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_4_2_2","unstructured":"CEDAX (ceftibuten). 2010. Pernix Therapeutics.LLC Gonzales LA"},{"key":"e_1_3_4_3_2","unstructured":"ISOCEF (ceftibuten) [summary of product characteristics]. 2007. RECORDATI Industria Chimica e Farmaceutica S.p.A. Milan Italy"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw282"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_4_6_2","unstructured":"European Committee on Antimicrobial Susceptibility Testing. 2024. Breakpoint tables for interpretation of MICs and zone diameters. Version 14.0. https:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Breakpoint_tables\/v_14.0_Breakpoint_Tables.pdf."},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01304-21"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00934-22"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0732-8893(91)90096-x"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600830910"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01099-23"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.2.356"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.2.359"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00087-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00087-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:01:23Z","timestamp":1756904483000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00087-25"}},"subtitle":[],"editor":[{"given":"Sarah","family":"Doernberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":12,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,3]]}},"alternative-id":["10.1128\/aac.00087-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00087-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"assertion":[{"value":"2025-02-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00087-25"}}