{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:32:37Z","timestamp":1783355557297,"version":"3.54.6"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100012737","name":"Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021704","name":"Administration for Strategic Preparedness and Response","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["75A50123C00050"],"award-info":[{"award-number":["75A50123C00050"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ledaborbactam is an investigational oral \u03b2-lactamase inhibitor that restores ceftibuten's activity against strains of Enterobacterales expressing ESBLs and serine carbapenemases, offering a potential oral therapeutic option for cUTIs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To characterize the activity of ceftibuten-ledaborbactam human simulated regimens (HSRs) against \u03b2-lactamase-producing Enterobacterales in a murine urinary tract infection (UTI) model assessing infection in both the kidney and bladder.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Ten urogenic Enterobacterales (ceftibuten-ledaborbactam MIC \u22640.03 to 4\u2005mg\/L; ESBL, KPC, OXA-48) were assessed. Murine HSRs for oral ceftibuten (400\u2005mg q8\u2005h and 600\u2005mg q12\u2005h) alone and combined with oral ledaborbactam (400\u2005mg q8\u2005h and 600\u2005mg q12\u2005h) were developed. Activity was assessed by absolute bacterial burden (log10 cfu) in kidneys and bladders after 24\u2005h of treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mean (\u00b1SD) bacterial burdens in kidneys and bladders of mice at the start of dosing (0\u2005h control) were 5.54\u200a\u00b1\u200a0.22 and 2.95\u200a\u00b1\u200a0.39 log10 cfu\/tissue, respectively, which increased to &amp;gt;9 and &amp;gt;5.5 log10 cfu\/tissue after 24\u2005h. Ceftibuten monotherapy demonstrated similar growth compared to saline-dosed controls. Ceftibuten-ledaborbactam activity resulted in bacterial burden ranging from 3.56 to 6.44 log10 cfu\/kidney for the q8\u2005h regimen and 4.09\u20135.94 log10 cfu\/kidney for the q12\u2005h regimen across nine isolates with MIC\u200a\u2264\u200a0.5\u2005mg\/L. In bladders, a bacterial burden of 2.00\u20133.92 log10 cfu was observed across treatment groups. As anticipated, the high MIC strain (4\u2005mg\/L), displayed only a moderate bacterial burden reduction in the kidney and bladder after treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>HSR exposures of ceftibuten-ledaborbactam administered q8\u2005h and q12\u2005h resulted in similar and marked bacterial reduction in an upper (kidney) and lower (bladder) UTI model caused by a variety of multi-drug resistant Enterobacterales.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf277","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T19:04:07Z","timestamp":1755025447000},"page":"2714-2718","source":"Crossref","is-referenced-by-count":2,"title":["<i>In vivo<\/i> activity of ceftibuten-ledaborbactam oral combination against serine-\u03b2-lactamase-producing Enterobacterales: an assessment in the pyelonephritis and cystitis murine model"],"prefix":"10.1093","volume":"80","author":[{"given":"Christina","family":"Koenig","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , 80 Seymour Street, Hartford, CT 06102 ,","place":["USA"]},{"name":"Department of Intensive Care Medicine, University Hospital Hamburg-Eppendorf , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yi","sequence":"additional","affiliation":[{"name":"Center for Diagnostic Innovation, Pathology and Lab Medicine, Children's Hospital of Philadelphia, PA 19104, USA, Previously with Venatorx Pharmaceuticals , Malvern, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , 80 Seymour Street, Hartford, CT 06102 ,","place":["USA"]},{"name":"Division of Infectious Diseases, Hartford Hospital , 80 Seymour Street, Hartford, CT 06102 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-0924","authenticated-orcid":false,"given":"Tomefa E","family":"Asempa","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , 80 Seymour Street, Hartford, CT 06102 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"2025100314241947900_dkaf277-B1","doi-asserted-by":"publisher","first-page":"ofw281","DOI":"10.1093\/ofid\/ofw281","article-title":"The increase in hospitalizations for urinary tract infections and the associated costs in the United States, 1998\u20132011","volume":"4","author":"Simmering","year":"2017","journal-title":"Open Forum Infect Dis"},{"key":"2025100314241947900_dkaf277-B2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary tract infections: epidemiology, mechanisms of infection and treatment options","volume":"13","author":"Flores-Mireles","year":"2015","journal-title":"Nat Rev Microbiol"},{"key":"2025100314241947900_dkaf277-B3","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/jhm.2157","article-title":"Impact of extended-spectrum beta-lactamase-producing organisms on clinical and economic outcomes in patients with urinary tract infection","volume":"9","author":"MacVane","year":"2014","journal-title":"J Hosp Med"},{"key":"2025100314241947900_dkaf277-B4","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1093\/cid\/cis534","article-title":"The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat?","volume":"55","author":"Cai","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2025100314241947900_dkaf277-B5","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1093\/cid\/civ696","article-title":"Asymptomatic bacteriuria treatment is associated with a higher prevalence of antibiotic resistant strains in women with urinary tract infections","volume":"61","author":"Cai","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2025100314241947900_dkaf277-B6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S0924-8579(03)00248-6","article-title":"Asymptomatic bacteriuria. 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