{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:23Z","timestamp":1791414143891,"version":"4.3.3"},"reference-count":43,"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":[{"DOI":"10.13039\/100000774","name":"DOD | Defense Threat Reduction Agency","doi-asserted-by":"crossref","award":["HDTRA1-07-9-0002"],"award-info":[{"award-number":["HDTRA1-07-9-0002"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"crossref"}]},{"name":"GlaxoSmithKline"}],"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              <jats:italic>Bacillus anthracis<\/jats:italic>\n              is a Gram-positive Centers for Disease Control and Prevention category \u201cA\u201d biothreat pathogen. Without early treatment, inhalation of anthrax spores with progression to inhalational anthrax disease is associated with high fatality rates. Gepotidacin is a novel first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and is being evaluated for use against biothreat and conventional pathogens. Gepotidacin selectively inhibits bacterial DNA replication via a unique binding mode and has\n              <jats:italic>in vitro<\/jats:italic>\n              activity against a collection of\n              <jats:italic>B. anthracis<\/jats:italic>\n              isolates including antibacterial-resistant strains, with the MIC\n              <jats:sub>90<\/jats:sub>\n              ranging from 0.5 to 1 \u00b5g\/mL.\n              <jats:italic>In vivo<\/jats:italic>\n              activity of gepotidacin was also evaluated in the New Zealand White rabbit model of inhalational anthrax. The primary endpoint was survival, with survival duration and bacterial clearance as secondary endpoints. The trigger for treatment was the presence of anthrax protective antigen in serum. New Zealand White rabbits were dosed intravenously for 5 days with saline or gepotidacin at 114 mg\/kg\/d to simulate a dosing regimen of 1,000 mg intravenous (i.v.) three times a day (TID) in humans. Gepotidacin provided a survival benefit compared to saline control, with 91% survival (\n              <jats:italic>P<\/jats:italic>\n              -value: 0.0001). All control animals succumbed to anthrax and were found to be blood- and organ culture-positive for\n              <jats:italic>B. anthracis<\/jats:italic>\n              . The novel mode of action,\n              <jats:italic>in vitro<\/jats:italic>\n              microbiology, preclinical safety, and animal model efficacy data, which were generated in line with Food and Drug Administration Animal Rule, support gepotidacin as a potential treatment for anthrax in an emergency biothreat situation.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01497-23","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T13:48:28Z","timestamp":1708004908000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy of therapeutically administered gepotidacin in a rabbit model of inhalational anthrax"],"prefix":"10.1128","volume":"68","author":[{"given":"Jamese J.","family":"Hilliard","sequence":"first","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4839-0266","authenticated-orcid":true,"given":"Charles","family":"Jakielaszek","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Mannino","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Hossain","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Qian","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2842-9063","authenticated-orcid":true,"given":"Cindy","family":"Fishman","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samandra","family":"Demons","sequence":"additional","affiliation":[{"name":"US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Hershfield","sequence":"additional","affiliation":[{"name":"US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Soffler","sequence":"additional","affiliation":[{"name":"US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Russo","sequence":"additional","affiliation":[{"name":"Rutgers University School of Medicine, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Henning","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center (BBRC), Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Novak","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center (BBRC), Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4168-9401","authenticated-orcid":false,"given":"Karen","family":"O'Dwyer","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins7083167"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300985810378112"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8030069"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.07.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.02.012"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2221-1691(11)60109-3"},{"key":"e_1_3_3_8_2","volume-title":"Anthrax in humans and animals","author":"World Health Organization","year":"2008","unstructured":"World Health Organization. 2008. 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