{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:01:44Z","timestamp":1791414104325,"version":"4.3.3"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Acurx Pharmaceuticals","award":["G0506119"],"award-info":[{"award-number":["G0506119"]}]},{"name":"NIH NLM Training Program","award":["T15LM007093"],"award-info":[{"award-number":["T15LM007093"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,3,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Antimicrobial resistance is emerging in clinical strains of\n              <jats:italic>Clostridioides difficile<\/jats:italic>\n              . Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent\n              <jats:italic>in vitro<\/jats:italic>\n              activity against wild-type, susceptible strains but its effect on\n              <jats:italic>C. difficile<\/jats:italic>\n              strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant\n              <jats:italic>C. difficile<\/jats:italic>\n              strains. The\n              <jats:italic>in vitro<\/jats:italic>\n              activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other\n              <jats:italic>C. difficile<\/jats:italic>\n              antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC\n              <jats:sub>50\/90<\/jats:sub>\n              values (\u00b5g\/mL) for evaluated\n              <jats:italic>C. difficile<\/jats:italic>\n              strains were 4\/8, compared with 2\/4 for VAN, 0.5\/1 for FDX, and 0.25\/4 for MTZ. IBZ MIC\n              <jats:sub>50\/90<\/jats:sub>\n              values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of\n              <jats:italic>C. difficile<\/jats:italic>\n              strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of\n              <jats:italic>C. difficile<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01621-23","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T19:42:44Z","timestamp":1708112564000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of\n            <i>Clostridioides difficile<\/i>"],"prefix":"10.1128","volume":"68","author":[{"given":"Eug\u00e9nie","family":"Bass\u00e8res","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn A.","family":"Eubank","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurshida","family":"Begum","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Jahangir","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhee","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh M.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris K.","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne J.","family":"Gonzales-Luna","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-7503","authenticated-orcid":false,"given":"Kevin W.","family":"Garey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801550"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab549"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz513"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad194"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39429-x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab365"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01797-x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2106516"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30614-5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofw275"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx299"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac492.021"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.06.017"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac096"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw548"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1721335"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.03591-14"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2023.2252331"},{"key":"e_1_3_2_20_2","volume-title":"Performance standards for antimicrobial susceptibility testing","year":"2023","unstructured":"Clinical Laboratory and Standards Institute. 2023. Performance standards for antimicrobial susceptibility testing. 33rd ed. CLSI Supplement M100. Wayne, Pennsylvania.","edition":"33"},{"key":"e_1_3_2_21_2","unstructured":"Data from the EUCAST MIC distribution website. Accessed 30 March 2023"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01420"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2478"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2022.01.004"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa134"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01621-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01621-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T14:05:47Z","timestamp":1709733947000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01621-23"}},"subtitle":[],"editor":[{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,6]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,6]]}},"alternative-id":["10.1128\/aac.01621-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01621-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,6]]},"assertion":[{"value":"2023-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01621-23"}}