{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:56:10Z","timestamp":1781938570201,"version":"3.54.5"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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":[[2026,1,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Gepotidacin is a novel first-in-class triazaacenaphthylene antibiotic developed for the treatment of uncomplicated gonorrhea and uncomplicated urinary tract infections (uUTIs). To support uUTI,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      pharmacokinetics (PK)\/pharmacodynamics (PD) studies have been conducted in the murine neutropenic thigh infection model evaluating gepotidacin against 17 isolates of\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      and 7 isolates of\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      having MICs of 0.25 to 16 \u00b5g\/mL. Exposure data were fit using a population PK model, and efficacy data were fit with an inhibitory effect sigmoid Imax model using free-drug area under the concentration-time curve (fAUC)\/MIC as the primary index. The ratios associated with response were determined for each isolate, and the median fAUC\/MIC (excluding strains with &lt;1-log of growth from baseline) was 13. To retain the data for all isolates, an exploratory analysis was conducted using different criteria to determine the target for strains with &lt;1-log of growth (6 of the 24 strains tested). While the median fAUC\/MIC was similar regardless of the criteria used, this analysis highlights the importance of critically reviewing PK\/PD data for trends related to isolate characteristics and\/or individual study outputs. As previously reported, the systemic targets determined from PK\/PD studies were applied to urine concentrations for probability of target attainment analyses, which led to successful clinical trials and regulatory approval for gepotidacin in the treatment of uUTI. However, further work is needed to confirm the translational validity of these approaches on a broader scale and their application in establishing PK\/PD targets for cystitis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01176-25","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:03:44Z","timestamp":1764932624000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetic and pharmacodynamic characterization of gepotidacin against\n                    <i>Escherichia coli<\/i>\n                    and\n                    <i>Klebsiella pneumoniae<\/i>\n                    in a neutropenic mouse thigh infection model"],"prefix":"10.1128","volume":"70","author":[{"given":"Christine M.","family":"Singley","sequence":"first","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Kurumaddali","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-7541","authenticated-orcid":true,"given":"Jennifer L.","family":"Hoover","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3432"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01977-19"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00315"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01525-22"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01640-24"},{"key":"e_1_3_3_8_2","unstructured":"GSK. 2025. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older [Press release]"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02196-7"},{"key":"e_1_3_3_10_2","unstructured":"GSK. 2024. GSK announces positive headline results from EAGLE-1 phase III trial for gepotidacin in uncomplicated urogenital gonorrhoaea (GC)[Press release]"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02307-18"},{"key":"e_1_3_3_12_2","volume-title":"CLSI guideline M23 (ISBN 978-1-68440-186-4)","author":"Clinical and Laboratory Standards Institute (CLSI)","year":"2023","unstructured":"Clinical and Laboratory Standards Institute (CLSI). 2023. Development of in vitro susceptibility test methods, breakpoints, and quality control parameters. In CLSI guideline M23 (ISBN 978-1-68440-186-4), 6th ed. Clinical and Laboratory Standards Institute, USA.","edition":"6"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00115-16"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00122-21"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20145949"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.009"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/ab131e"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9133-0"},{"key":"e_1_3_3_19_2","volume-title":"Understanding pharmacokinetics (PK) and pharmacodynamics (PD)","author":"CLSI","year":"2018","unstructured":"CLSI. 2018. Understanding pharmacokinetics (PK) and pharmacodynamics (PD). Vol. 3."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00067-15"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.691210"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01492-21"},{"key":"e_1_3_3_23_2","unstructured":"U.S. Food and Drug Administration. 2025. FDA antibacterial susceptibility test interpretive criteria for gepotidacin. Silver Spring (MD): U.S. Food and Drug Administration. Available from: https:\/\/www.fda.gov\/drugs\/development-resources\/gepotidacin-oral-products"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/146.5.691"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01176-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01176-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:01:33Z","timestamp":1767794493000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01176-25"}},"subtitle":[],"editor":[{"given":"Vincent H.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,7]]}},"alternative-id":["10.1128\/aac.01176-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01176-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"assertion":[{"value":"2025-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01176-25"}}