{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:23:37Z","timestamp":1788269017143,"version":"build-2803163510"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100020955","name":"GlaxoSmithKline Biologicals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020955","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"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 that inhibits bacterial DNA replication through a distinct binding site and unique mechanism of action that provides well-balanced inhibition of two different type II topoisomerase enzymes (DNA gyrase and topoisomerase IV) for most pathogens. Gepotidacin was recently approved by the US Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for the treatment of uncomplicated urinary tract infections (uUTI) and by the FDA for uncomplicated urogenital gonorrhea. This study investigated the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      time-kill kinetics, post-antibiotic effect (PAE), and sub-inhibitory MIC effect (PAE-SME) of gepotidacin, as well as interactions between gepotidacin and select marketed antibacterial agents for species where the published activity of gepotidacin was limited. Species included are those known to be associated with uUTI:\n                      <jats:italic toggle=\"yes\">Citrobacter freundii<\/jats:italic>\n                      species complex,\n                      <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                      species complex,\n                      <jats:italic toggle=\"yes\">Klebsiella aerogenes<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Proteus mirabilis<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Providencia rettgeri<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Staphylococcus saprophyticus<\/jats:italic>\n                      . Isolates were selected to represent various phenotypes, including wild type, extended-spectrum beta-lactamase positive (ESBL), and fluoroquinolone-resistant. Gepotidacin displayed concentration-dependent activity in time-kill, PAE, and PAE-SME experiments. Gepotidacin displayed bactericidal activity, often by 8 h, against 83% of isolates when tested at 4\u00d7 and 10\u00d7 MIC. In general, modest PAEs (&gt;1\u20134 h) and extended PAE-SMEs (&gt;4 h) were observed for gepotidacin. No antagonism was observed in broth microdilution checkerboard studies with marketed antibiotics, and the only consistent synergy observed was with gepotidacin and vancomycin against\n                      <jats:italic toggle=\"yes\">S. saprophyticus<\/jats:italic>\n                      . These data add to the understanding of pharmacodynamics at play when treating with gepotidacin relevant uUTI species other than\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Antibiotic resistance continues to limit treatment options for common infections such as urinary tract infections (UTIs). Gepotidacin is a recently approved antibiotic that works in a new way compared with existing drugs, allowing it to remain active against bacteria that are resistant to many commonly used treatments. In this study, we examined how effectively gepotidacin kills several bacterial species that cause UTIs, including organisms that are resistant to fluoroquinolones or produce extended-spectrum \u03b2-lactamases. Gepotidacin was shown to rapidly reduce bacterial populations at clinically relevant concentrations and continued to suppress bacterial growth even after short exposures. Importantly, gepotidacin did not interfere with the activity of other commonly used antibiotics, suggesting it can potentially be used alongside existing therapies if needed. These findings provide additional evidence supporting the effectiveness of gepotidacin against a broad range of UTI pathogens and help improve our understanding of how this new antibiotic may perform in clinical treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00903-26","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:00:45Z","timestamp":1786021245000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of gepotidacin activity, including\n                    <i>in vitro<\/i>\n                    kill kinetics, checkerboard, and PAE\/SME testing against gram-positive and gram-negative bacteria"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-6238","authenticated-orcid":true,"given":"S. J. Ryan","family":"Arends","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"West","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4211-8261","authenticated-orcid":true,"given":"Nicole E.","family":"Scangarella-Oman","sequence":"additional","affiliation":[{"name":"GSK","place":["Collegeville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1782","authenticated-orcid":true,"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-1137","authenticated-orcid":true,"given":"Rodrigo E.","family":"Mendes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qv6pw23","id-type":"ROR","asserted-by":"publisher"}],"name":"Element Iowa City (JMI Laboratories)","place":["North Liberty, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00315"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.3c00346"},{"key":"e_1_3_4_5_2","unstructured":"U.S. Food and Drug Administration. 2025. BLUJEPA (gepotidacin) tablets for oral use: prescribing information. U.S. Food and Drug Administration Silver Spring MD. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/218230s000lbl.pdf. Retrieved 28 Jul 2026."},{"key":"e_1_3_4_6_2","unstructured":"Medicines and Healthcare products Regulatory Agency. 2025. MHRA approves UK\u2019s first new type of antibiotic for urinary tract infections in nearly 30 years. 28 August 2025. Available from: https:\/\/www.gov.uk\/government\/news\/mhra-approves-uks-first-new-type-of-antibiotic-for-urinary-tract-infections-in-nearly-30-years. Retrieved 28 Jul 2026."},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00628-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00468-17"},{"key":"e_1_3_4_9_2","volume-title":"1st Annual American Society for Microbiology General Meeting (MICROBE)","author":"Farrell DJ","year":"2016","unstructured":"Farrell DJ, Sader HS, Rhomberg PR, Scangarella-Oman NE, Flamm RK. 2016. Gepotidacin (GSK2140944) in vitro activity against Neisseria gonorrhoeae (MIC\/MBC, kill kinetics, checkerboard, PAE\/SME tests). 1st Annual American Society for Microbiology General Meeting (MICROBE). ASM Microbe, Boston, MA"},{"key":"e_1_3_4_10_2","unstructured":"U.S. Food and Drug Administration. 2025. Gepotidacin \u2013 oral products. U.S. Food and Drug Administration. Available from: https:\/\/www.fda.gov\/drugs\/development-resources\/gepotidacin-oral-products"},{"key":"e_1_3_4_11_2","volume-title":"M07-A7, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard","author":"Clinical and Laboratory Standards Institute","year":"2006","unstructured":"Clinical and Laboratory Standards Institute. 2006. M07-A7, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. 7th ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"7"},{"key":"e_1_3_4_12_2","volume-title":"M100Ed33. Performance standards for antimicrobial susceptibility testing","author":"Clinical & Laboratory Standards Institute","year":"2023","unstructured":"Clinical & Laboratory Standards Institute. 2023. M100Ed33. Performance standards for antimicrobial susceptibility testing. 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