{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:54:51Z","timestamp":1791924891291,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VenatoRx Pharmaceuticals Inc."},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012737","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["HHSN272201300019C"],"award-info":[{"award-number":["HHSN272201300019C"]}],"id":[{"id":"10.13039\/100012737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT101999\/Z\/13\/Z"],"award-info":[{"award-number":["WT101999\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Taniborbactam (VNRX-5133) is a novel boronate-based \u03b2-lactamase inhibitor that directly inhibits all four classes of \u03b2-lactamases. We studied the pharmacodynamics of taniborbactam in combination with cefepime against \u03b2-lactamase\u2013producing Enterobacterales and Pseudomonas aeruginosa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro, cefepime\/taniborbactam combination was assessed with a checkerboard broth microdilution method against two ESBL-producing Enterobacterales and one AmpC- and one VIM-producing P. aeruginosa isolates (cefepime MIC 16\u2013256 mg\/L). In vivo, neutropenic infected mice were treated with cefepime, every 2 h for 24 h, alone or in combination with taniborbactam at q2h, q4h and q8h dosing intervals. Single dose escalation and dose-fractionation experiments were conducted in order to describe plasma pharmacokinetics and pharmacodynamics of taniborbactam, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro, reversal of phenotypic resistance to cefepime was found at taniborbactam \u22640.03 and 0.25 mg\/L for ESBL-producing E. coli and K. pneumoniae, and at 0.125 and 2 mg\/L for VIM- and AmpC constitutively-producing P. aeruginosa, respectively. In vivo, cefepime alone marginally reached stasis against Enterobacterales and AmpC-producing P. aeruginosa. Taniborbactam restored cefepime\u2019s static effect against all isolates and its 1 log10 kill effect against all strains except the K. pneumoniae isolate. The percentage of time above free concentration threshold (%fT\u200a&amp;gt;\u200aCt) best described taniborbactam efficacy (R2 = 0.50\u20130.80). At high cefepime exposures, area under the free concentration\u2013time curve (fAUC) performed equally well (R2 0.49\u20130.70). A 40%\u201350% and 60%\u2013100% fT\u200a&amp;gt;\u200aCt of taniborbactam was associated with stasis and 1 log10 kill, respectively, at taniborbactam concentrations where reversal of cefepime resistance was found in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taniborbactam restored cefepime\u2019s activity against resistant Gram-negative bacteria in a time- and concentration-dependent manner at low and higher cefepime exposures, respectively.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf431","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:54:17Z","timestamp":1762865657000},"source":"Crossref","is-referenced-by-count":3,"title":["Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against \u03b2-lactamase\u2013producing Gram-negative bacteria in a neutropenic murine thigh infection model"],"prefix":"10.1093","volume":"81","author":[{"given":"Panagiota-Christina","family":"Georgiou","sequence":"first","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Rimini 1, Haidari, Athens 12462 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-1007","authenticated-orcid":false,"given":"Maria","family":"Siopi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Rimini 1, Haidari, Athens 12462 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Tsala","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Rimini 1, Haidari, Athens 12462 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lagarde","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Radboud University, Nijmegen Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Kloezen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-6251","authenticated-orcid":false,"given":"Anouk E","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center , Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Medical Microbiology, Haaglanden Medisch Centrum , The Hague ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8869-1509","authenticated-orcid":false,"given":"Joseph","family":"Meletiadis","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Rimini 1, Haidari, Athens 12462 ,","place":["Greece"]},{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"2026011413275736200_dkaf431-B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","article-title":"Attributable deaths and disability-adjusted life-years caused by infections with 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