{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:46:26Z","timestamp":1790646386895,"version":"4.1.0"},"reference-count":15,"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 (LED-E), a novel oral prodrug that converts to the active \u03b2-lactamase inhibitor (BLI) ledaborbactam (LED), is being developed in combination with ceftibuten (CTB) to address a need for oral treatments against drug-resistant Enterobacterales infections. Two Phase 1 studies were conducted to (i) evaluate the safety and pharmacokinetics of single doses of LED-E 100 to 1000 mg and multiple doses of LED-E 75 to 500 mg every 8 h (q8h) for 10 days, (ii) assess potential drug interactions between CTB and LED, and (iii) evaluate safety and pharmacokinetics following multiple doses of LED-E 300 or 500 mg with CTB 400 mg or placebo q8h for 10 days. Treatment-emergent adverse events (TEAEs) were reported for 82% LED-E \u00b1 CTB (\n              <jats:italic toggle=\"yes\">n<\/jats:italic>\n              = 109) and 78% placebo (\n              <jats:italic toggle=\"yes\">n<\/jats:italic>\n              =27) participants, respectively. TEAEs of gastrointestinal disorders were reported for 28% of the LED-E \u00b1 CTB and 15% of placebo participants. Following single doses, LED-E AUC\n              <jats:sub>inf<\/jats:sub>\n              was less than 2% of LED exposures, demonstrating extensive conversion to active BLI. LED AUC increased dose proportionally following single LED doses and less than proportionally following multiple LED-E doses. After 10 days of q8h dosing, the LED terminal half-life in plasma was approximately 11 to 12 h. Steady-state urinary excretion of LED-E\u2013derived material (comprised almost entirely of unchanged LED) was 84%. No clinically relevant CTB and LED PK interactions occurred with the CTB + LED-E combination. These results support further development of the CTB + LED-E combination for the treatment of complicated urinary tract infections caused by drug-resistant Enterobacterales.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>CLINICAL TRIALS<\/jats:title>\n              <jats:p>\n                These studies are registered with ClinicalTrials.gov as\n                <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04243863\" 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\/NCT04243863\">NCT04243863<\/jats:related-object>\n                and\n                <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04877379\" 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\/NCT04877379\">NCT04877379<\/jats:related-object>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aac.00210-25","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T20:14:57Z","timestamp":1755202497000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Safety and pharmacokinetics of single and multiple doses of ledaborbactam etzadroxil with or without ceftibuten in healthy volunteers"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4989-4896","authenticated-orcid":false,"given":"Carlos Fernando","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth","family":"Dorr","sequence":"additional","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"van de Wetering","sequence":"additional","affiliation":[{"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","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_4_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. WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. World Health Organization, Geneva."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12111590"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy378"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00552-21"},{"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":"10.1093\/jac\/dkab425"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00437"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01127-24"},{"key":"e_1_3_4_12_2","unstructured":"ISOCEF (ceftibuten) [summary of product characteristics]. 2007. Milan Italy RECORDATI Industria Chimica e Farmaceutica S.p.A"},{"key":"e_1_3_4_13_2","unstructured":"CEDAX (ceftibuten) [product information]. 2010. Pernix Therapeutics LLC Gonzales LA"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac359"},{"key":"e_1_3_4_15_2","unstructured":"Asempa TE K\u00f6nig C Yi F Nicolau DP. 2025. In vivo efficacy of ceftibuten-ledaborbactamhuman-simulated oral exposures against ESBL-and carbapenemase producing Enterobacterales in the murine urinary tract infection model (UTI). American Society for Microbiology Microbe"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1026451721686"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00210-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00210-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:02:06Z","timestamp":1756904526000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00210-25"}},"subtitle":[],"editor":[{"given":"Sarah","family":"Doernberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,3]]}},"alternative-id":["10.1128\/aac.00210-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00210-25","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":"2025-02-16","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":"e00210-25"}}