{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:37Z","timestamp":1785403777294,"version":"3.56.0"},"reference-count":19,"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\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["HHSO100201900007C"],"award-info":[{"award-number":["HHSO100201900007C"]}],"id":[{"id":"10.13039\/100012399","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":"ABSTRACT<\/jats:title>\n \n \n \n Taniborbactam is a novel cyclic boronate \u03b2-lactamase inhibitor that potentiates the\n in vitro<\/jats:italic>\n activity of cefepime against Enterobacterales and\n Pseudomonas aeruginosa<\/jats:italic>\n strains harboring serine and metallo-\u03b2-lactamases. Taniborbactam lacks intrinsic antibacterial activity. An\n in vitro<\/jats:italic>\n hollow fiber infection model (HFIM) was used to evaluate bacterial kill and the potential for treatment-emergent resistance associated with the clinical cefepime-taniborbactam dose of 2\u20130.5 g every 8 h, administered as a 2 h infusion, for 7 days. Nine cefepime-resistant bacterial strains were studied among one\n Escherichia coli<\/jats:italic>\n , five\n Klebsiella pneumoniae<\/jats:italic>\n , and three\n P. aeruginosa<\/jats:italic>\n that harbored a variety of cephalosporinases, extended-spectrum \u03b2-lactamases, and carbapenemases with cefepime-taniborbactam MIC values that ranged from 0.25 to 8 \u00b5g\/mL. All nine strains grew rapidly when treated with cefepime alone, consistent with phenotypic resistance. Human plasma concentration-time profiles for cefepime and taniborbactam were simulated in the HFIM systems and resulted in bactericidal activity (\u22653 log\n 10<\/jats:sub>\n CFU\/mL reduction) against eight of nine strains when assessed 8 h after initiation of the first dose, and against all nine strains by day 7. Treatment-emergent resistance, defined as bacterial subpopulations with \u22654 times the baseline MIC, was not detected in any cefepime-taniborbactam model from days 1 to 7. Therefore, human cefepime-taniborbactam exposures demonstrated sustained bactericidal activity and suppressed the emergence of resistance in a 7-day HFIM among serine and metallo-\u03b2-lactamase-positive Enterobacterales and\n P. aeruginosa<\/jats:italic>\n strains. These observations support the clinical development of cefepime-taniborbactam and inform understanding of its potential role in treating serine and\/or metallo-\u03b2-lactamase-positive Gram-negative bacterial infections.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/aac.00017-25","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:56:59Z","timestamp":1753963019000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Assessment of human exposures of cefepime-taniborbactam against cefepime-resistant Enterobacterales and\n Pseudomonas aeruginosa<\/i>\n in a 7-day hollow fiber infection model"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0400-4459","authenticated-orcid":true,"given":"Lindsay M.","family":"Avery","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Edwards","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7827-7227","authenticated-orcid":true,"given":"Greg","family":"Moeck","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6994-4286","authenticated-orcid":true,"given":"Tsuyoshi","family":"Uehara","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Venatorx Pharmaceuticals, Inc.","place":["Malvern, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Pevear","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s3j1d69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, 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","unstructured":"WHO Bacterial Priority Pathogens List. 2024. Bacterial pathogens of public health importance to guide research development and strategies to prevent and control antimicrobial resistance. License: CC BY-NC-SA 3.0 IGO. Geneva World Health Organization."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01963-19"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa373"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab405"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304748"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02307-18"},{"key":"e_1_3_4_9_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically","author":"Clinical and Laboratory Standards Institute","year":"2024","unstructured":"Clinical and Laboratory Standards Institute. 2024. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard M7-Ed12. Clinical and Laboratory Standards Institute, Wayne PA, USA.","edition":"7"},{"key":"e_1_3_4_10_2","series-title":"CLSI Supplement M100","volume-title":"Performance standards for antimicrobial susceptibility testing","author":"Clinical and Laboratory Standards Institute","year":"2024","unstructured":"Clinical and Laboratory Standards Institute. 2024. Performance standards for antimicrobial susceptibility testing. 34th ed. CLSI Supplement M100. Clinical and Laboratory Standards Institute, Wayne, PA, USA.","edition":"34"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00253-22"},{"key":"e_1_3_4_12_2","unstructured":"Abbvie Inc. 2015. AVYCAZ (ceftazidime and avibactam) for injection for intravenous use. Initial U.S. Approval: 2015"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01969-17"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05005-11"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14071485"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00065-10"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac425"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae063"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac183"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00461-13"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00017-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00017-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:02:00Z","timestamp":1756904520000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00017-25"}},"subtitle":[],"editor":[{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,3]]}},"alternative-id":["10.1128\/aac.00017-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00017-25","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":"2025-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00017-25"}}