{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:45:31Z","timestamp":1791229531059,"version":"4.1.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201600029C"],"award-info":[{"award-number":["HHSN272201600029C"]}],"id":[{"id":"10.13039\/100006492","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":[[2022,11,15]]},"abstract":"<jats:p>\n            Ceftibuten-ledaborbactam etzadroxil is a cephalosporin-boronate \u03b2-lactamase inhibitor prodrug combination under development as an oral treatment for complicated urinary tract infections caused by multidrug-resistant (MDR)\n            <jats:italic>Enterobacterales<\/jats:italic>\n            producing serine \u03b2-lactamases (Ambler class A, C, and D).\n            <jats:italic>In vivo<\/jats:italic>\n            , ledaborbactam etzadroxil (formerly VNRX-7145) is cleaved to the active inhibitor ledaborbactam (formerly VNRX-5236). To more completely define the breadth of ceftibuten-ledaborbactam\u2019s activity against important antimicrobial-resistant pathogens, we assessed its\n            <jats:italic>in vitro<\/jats:italic>\n            activity against phenotypic and genotypic subsets from a 2018\u20132020 global culture collection of 3,889 clinical isolates of\n            <jats:italic>Enterobacterales<\/jats:italic>\n            , including MDR organisms, extended-spectrum-\u03b2-lactamase (ESBL)-positive organisms, and organisms that are nonsusceptible and resistant to other antimicrobials.\n          <\/jats:p>","DOI":"10.1128\/aac.00934-22","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T13:01:37Z","timestamp":1666789297000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Ceftibuten-Ledaborbactam Activity against Multidrug-Resistant and Extended-Spectrum-\u03b2-Lactamase-Positive Clinical Isolates of\n            <i>Enterobacterales<\/i>\n            from a 2018\u20132020 Global Surveillance Collection"],"prefix":"10.1128","volume":"66","author":[{"given":"James A.","family":"Karlowsky","sequence":"first","affiliation":[{"name":"IHMA, Schaumburg, Illinois, USA"},{"name":"Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-1851","authenticated-orcid":true,"given":"Mark G.","family":"Wise","sequence":"additional","affiliation":[{"name":"IHMA, Schaumburg, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith A.","family":"Hackel","sequence":"additional","affiliation":[{"name":"IHMA, Schaumburg, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Pevear","sequence":"additional","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Moeck","sequence":"additional","affiliation":[{"name":"Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Sahm","sequence":"additional","affiliation":[{"name":"IHMA, Schaumburg, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00047-19"},{"key":"e_1_3_3_3_2","unstructured":"Centers for Disease Control and Prevention. 2019. Antibiotic resistance threats in the United States 2019. https:\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf."},{"key":"e_1_3_3_4_2","unstructured":"World Health Organization. 2017. Global priority list of antibiotic-resistant bacteria to guide research discovery and development of new antibiotics. https:\/\/www.who.int\/news\/item\/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed. Accessed 17 October 2022."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0159-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00021-21"},{"key":"e_1_3_3_7_2","unstructured":"World Health Organization. 2020. Target product profiles for oral therapy of urinary tract infections. https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/332250\/9789240003873-eng.pdf?ua=1."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00552-21"},{"key":"e_1_3_3_9_2","unstructured":"John KJ Chatwin CL Hamrick JC Moeck G Pevear DC. 2019. Rescue of ceftibuten activity by the oral \u03b2-lactamase inhibitor VNRX-7145 against Enterobacteriaceae expressing class A C and\/or D \u03b2-lactamases poster AAR-719. Abstr ASM MICROBE 2019 San Francisco CA."},{"key":"e_1_3_3_10_2","unstructured":"Myers CL Daigle DM Burns CJ Pevear DC. 2019. Ceftibuten\/VNRX-7145 an orally bioavailable \u03b2-lactam\/\u03b2-lactamase inhibitor combination active against serine-\u03b2-lactamase-producing Enterobacteriaceae poster P1182. Abstr ECCMID 2019 Amsterdam the Netherlands."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00437"},{"key":"e_1_3_3_12_2","unstructured":"Chatwin CL Hamrick JC John KJ Burns CJ Xerri L Moeck G Pevear DC. 2019. Selection of ceftibuten as the partner antibiotic for the oral \u03b2-lactamase inhibitor VNRX-7145 poster P1181. Abstr ECCMID 2019 Amsterdam the Netherlands."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01304-21"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab425"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_3_16_2","volume-title":"Performance standards for antimicrobial susceptibility testing; M100","author":"Clinical and Laboratory Standards Institute","year":"2022","unstructured":"Clinical and Laboratory Standards Institute. 2022. Performance standards for antimicrobial susceptibility testing; M100, 32nd ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"32"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02385-20"},{"key":"e_1_3_3_18_2","unstructured":"EUCAST. 2022. EUCAST breakpoint tables for interpretation of MICs and zone diameters. Version 12.0. http:\/\/www.eucast.org\/clinical_breakpoints\/."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-020-0362-4"},{"key":"e_1_3_3_20_2","unstructured":"Hamrick JC Chatwin CL John KJ Burns CJ Xerri L Moeck G Pevear DC. 2019. Oral ceftibuten\/VNRX-7145 shows comparable activity in vitro to IV therapeutics against MDR Enterobacteriaceae poster P1183. Abstr ECCMID 2019 Amsterdam the Netherlands."},{"key":"e_1_3_3_21_2","unstructured":"Uehara T Chatwin CL Miller B Hamrick JC Six DA Moeck G Burns CJ Pevear DC Daigle DM. 2020. Spectrum of \u03b2-lactamase coverage by ceftibuten\/VNRX-7145 defined in engineered Escherichia coli. Abstr ASM MICROBE 2020 Chicago IL."},{"key":"e_1_3_3_22_2","unstructured":"Uehara T Miller B Chatwin CL Hamrick JC Six DA Moeck G Burns CJ Pevear DC Daigle DM. 2020. Impact of porin and efflux changes on the activity of ceftibuten\/VNRX-7145 in Klebsiella pneumoniae. Abstr ASM MICROBE 2020 Chicago IL."},{"key":"e_1_3_3_23_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; M07","author":"Clinical and Laboratory Standards Institute","year":"2018","unstructured":"Clinical and Laboratory Standards Institute. 2018. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; M07, 11th ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"11"},{"key":"e_1_3_3_24_2","unstructured":"Avery LM Abdelraouf K Nicolau DP. 2019. Assessment of the in vivo pharmacodynamics profile of ceftibuten (CTB)\/VNRX-7145 combination against serine \u03b2-lactamase-producing Enterobacteriaceae (SBL-EB) in the neutropenic murine thigh infection model poster AAR-727. 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