{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:12:04Z","timestamp":1792699924626,"version":"4.5.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Gepotidacin, a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial, was noninferior to nitrofurantoin in two pivotal trials (EAGLE-2 and EAGLE-3) in females with uncomplicated urinary tract infections (uUTIs). Using pooled data, gepotidacin\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              activity and clinical efficacy were evaluated for subsets of molecularly characterized isolates in the microbiological Intent-to-Treat population. The subsets of isolates were characterized based on phenotypic\/MIC criteria; all microbiological failure isolates were also characterized. Of 1,159\n              <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n              isolates\n              <jats:italic toggle=\"yes\">,<\/jats:italic>\n              30% harbored quinolone resistance-determining region (QRDR) mutations; most prevalent was\n              <jats:italic toggle=\"yes\">gyrA<\/jats:italic>\n              S83L, D87N (27%). Extended-spectrum \u03b2-lactamases (ESBLs) were detected in 13% of\n              <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n              isolates. For 114\n              <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n              isolates, 22% were plasmid-mediated quinolone resistance (PMQR) gene-positive, 11% had QRDR mutations, and 12% had ESBLs. Among 67\n              <jats:italic toggle=\"yes\">Proteus mirabilis<\/jats:italic>\n              isolates, 21% harbored QRDR mutations. Gepotidacin MIC\n              <jats:sub>90<\/jats:sub>\n              values ranged from 1 to 32 \u00b5g\/mL against qualifying Enterobacterales uropathogens and genotypic subcategories, with no isolates considered resistant to gepotidacin. For all genotypic subcategories, gepotidacin MIC\n              <jats:sub>90<\/jats:sub>\n              values were similar (i.e., lower, equal to, or 1-dilution higher) compared with the overall species (4 \u00b5g\/mL), with the exception of\n              <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n              isolates with the PMQR\n              <jats:italic toggle=\"yes\">qnrS1<\/jats:italic>\n              gene (16 \u00b5g\/mL); all were gepotidacin-susceptible. For the majority of uropathogens, including those with genotypes likely to cause resistance to standard uUTI therapies, success rates for gepotidacin were similar across genotypic subcategories for each species. These data show gepotidacin\u2019s efficacy and\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              activity against a wide range of uropathogen genotypes. Additionally, these pooled results provide a robust, contemporary data set and insight into current genotypic mechanisms of resistance.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>CLINICAL TRIALS<\/jats:title>\n              <jats:p>\n                This study is registered with ClinicalTrials.gov as\n                <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04020341\" document-id-type=\"clinical-trial-number\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04020341\">NCT04020341<\/jats:related-object>\n                and\n                <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT04187144\" document-id-type=\"clinical-trial-number\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04187144\">NCT04187144<\/jats:related-object>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aac.01639-24","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T14:42:37Z","timestamp":1757428957000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and\n            <i>in vitro<\/i>\n            activity of gepotidacin against bacterial uropathogens, including subsets with molecularly characterized resistance mechanisms and genotypes\/epidemiological clones, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3)"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4211-8261","authenticated-orcid":true,"given":"Nicole E.","family":"Scangarella-Oman","sequence":"first","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"Butler","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Breton","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrek","family":"Brown","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Kasapidis","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3115-5016","authenticated-orcid":false,"given":"Amanda J.","family":"Sheets","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13756-022-01121-y"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq257"},{"key":"e_1_3_4_4_2","unstructured":"National Institute for Health and Care Excellence. 2018. Urinary tract infection (lower): antimicrobial prescribing. Available from: https:\/\/www.nice.org.uk\/guidance\/ng109\/resources\/urinary-tract-infection-lower-antimicrobial-prescribing-pdf-66141546350533"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.03.035"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11050627"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3432"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02824-14"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00125-13"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01852.x"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2013.10.002"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2006.05.238"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.13.12"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00315"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.3c00346"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00207-19"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01525-22"},{"key":"e_1_3_4_19_2","volume-title":"Abstr 29th ECCMID","author":"Mushtaq S","year":"2019","unstructured":"Mushtaq S, Vickers A, Sadouki Z, Cole M, Fifer H, Donascimento V, Day M, Pinna E, Jenkins C, Godbole G, Woodford N. 2019. In vitro activities of gepotidacin, a novel triazaacenaphthylene and topoisomerase IV DNA gyrase inhibitor, against Gram-negative bacteria and Staphylococcus saprophyticus, poster P1849. Abstr 29th ECCMID; Amsterdam, The Netherlands"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02196-7"},{"key":"e_1_3_4_21_2","unstructured":"Blujepa (gepotidacin). 2025. Package Insert. GSK"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"Scangarella-Oman NE Butler DL Breton J Brown D Kasapidis C Millns H Huang C Perry CR Sheets AJ Dennison J Janmohamed S. 2025. Efficacy and in vitro activity of gepotidacin against bacterial uropathogens including drug-resistant phenotypes in females with uncomplicated urinary tract infections: results from two global pivotal phase 3 trials (EAGLE-2 and EAGLE-3). Antimicrob Agents Chemother. in press.","DOI":"10.1128\/aac.01640-24"},{"key":"e_1_3_4_23_2","unstructured":"Food and Drug Administration. 2025. Antibacterial susceptibility test interpretive criteria. Available from: https:\/\/www.fda.gov\/drugs\/development-resources\/antibacterial-susceptibility-test-interpretive-criteria. Retrieved 14 Apr 2025."},{"key":"e_1_3_4_24_2","unstructured":"Centers for Disease Control and Prevention. 2019. Antibiotic resistance threats in the United States 2019. Available from: https:\/\/www.cdc.gov\/antimicrobial-resistance\/media\/pdfs\/2019-ar-threats-report-508.pdf?CDC_AAref_Val=https:\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf"},{"key":"e_1_3_4_25_2","unstructured":"World Health Organization. 2024. World Health Organization. WHO bacterial priority pathogens list 2024: bacterial pathogens of public health importance to guide research development and strategies to prevent and control antimicrobial resistance. Available from: https:\/\/iris.who.int\/handle\/10665\/376776"},{"key":"e_1_3_4_26_2","unstructured":"Mendes RE Beekman D Scullin A Karr M Kapoor R Torumkuney D Arends SJR. 2024. In vitro activity of gepotidacin tested against molecularly characterized Escherichia coli isolates responsible for urinary tract infections in the US (2019\u20132022) poster P1060. Los Angeles CA IDWEEK. https:\/\/gskusmedicalaffairs.com\/docviewer.html?cmd=GSKMedicalInformation&medcommid=REF--ALL-006147&token=23108-d8b1e2b5-f3c8-4fc9-8451-eb10c030be5c&dns=gsk-medcomms.veevavault.com."},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-022-00706-9"},{"key":"e_1_3_4_28_2","volume-title":"M07Ed11Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically","author":"Clinical and Laboratory Standards Institute","year":"2018","unstructured":"Clinical and Laboratory Standards Institute. 2018. M07Ed11. 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American Society for Microbiology, Washington, DC."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01639-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01639-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T13:01:45Z","timestamp":1759323705000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01639-24"}},"subtitle":[],"editor":[{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1128\/aac.01639-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01639-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01639-24"}}