{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:04:59Z","timestamp":1790697899967,"version":"4.1.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Uncomplicated urinary tract infections (uUTIs) are common infections in women, and symptoms negatively impact patients\u2019 quality of life. Rapid symptom improvement is a high priority for patients and health care practitioners; however, few studies describe the early clinical effects of treatment.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate clinical symptom improvement daily from 24 hours until end of gepotidacin treatment (96 hours) and on day 10 in females with uUTIs.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This phase 3b, open-label, single-arm, multicenter nonrandomized clinical trial (October 2, 2024, to March 10, 2025) screened females (aged \u226512 years) with 2 or more uUTI symptoms and urinary nitrites or pyuria at 21 US sites.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Oral gepotidacin (1500 mg) twice daily for 5 days.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was clinical symptom improvement (decrease in total clinical symptom score [CSS] of \u22651 from baseline without other systemic antimicrobials, with or without resolution) at 24 (\u00b14) hours after treatment initiation. Secondary outcomes were clinical symptom improvement at 48, 72, and 96 (all \u00b14) hours after treatment initiation, clinical symptom resolution (reduction in total CSS to 0 without other systemic antimicrobials) at 24, 48, 72, and 96 (all \u00b14) hours after treatment initiation, and safety. Exploratory outcome was clinical symptom improvement and resolution at day 10 (+3 days).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Overall, 103 females were evaluated, with 97 enrolling, 96 completing the study, 93 completing the study treatment, and 90 (mean [SD] age, 46.1 [16.4] years) included in the clinically evaluable population for the primary outcome. At 24 hours, 49 participants (54.4%; 95% CI, 43.6%-65.0%) in the clinically evaluable population had clinical symptom improvement. The number of participants with clinical symptom improvement at 48, 72, and 96 hours was 71 of 89 (79.8%; 95% CI, 69.9%-87.6%), 81 of 90 (90.0%; 95% CI, 81.9%-95.3%), and 77 of 89 (86.5%; 95% CI, 77.6%-92.8%), respectively. Clinical symptom resolution increased from 3 of 90 patients (3.3%) at 24 hours to 81 of 90 (90.0%) at day 10. Fifty-eight adverse events, mostly mild or moderate, were reported in 27 participants from the safety population. There were no serious adverse events.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this phase 3b nonrandomized clinical trial, female participants with uUTIs experienced a rapid clinical response to gepotidacin as early as 24 hours after treatment initiation. These data may aid informed decision-making in the use of gepotidacin for treating uUTIs.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT06597344<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.34116","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:30:25Z","timestamp":1790695825000},"page":"e2634116","source":"Crossref","is-referenced-by-count":0,"title":["Gepotidacin and Early Symptom Improvement in Uncomplicated Urinary Tract Infection"],"prefix":"10.1001","volume":"9","author":[{"given":"Marcela","family":"Ram\u00edrez","sequence":"first","affiliation":[{"name":"GSK, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Gupta","sequence":"additional","affiliation":[{"name":"Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jazm\u00edn","family":"D\u00edaz-Rega\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"GSK, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudrani","family":"Banerjee","sequence":"additional","affiliation":[{"name":"GSK, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagriti","family":"Bablani","sequence":"additional","affiliation":[{"name":"GSK, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Powell","sequence":"additional","affiliation":[{"name":"GSK, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene","family":"Hankinson","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Janmohamed","sequence":"additional","affiliation":[{"name":"GSK, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"zoi260926r1","doi-asserted-by":"publisher","DOI":"10.1177\/1756287219832172","article-title":"An introduction to the epidemiology and burden of urinary tract infections.","volume":"11","author":"Medina","year":"2019","journal-title":"Ther Adv Urol"},{"issue":"1","key":"zoi260926r3","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s12905-022-01757-3","article-title":"The emotional impact of urinary tract infections in women: a qualitative analysis.","volume":"22","author":"Grigoryan","year":"2022","journal-title":"BMC Womens Health"},{"issue":"725","key":"zoi260926r4","doi-asserted-by":"publisher","first-page":"e882","DOI":"10.3399\/BJGP.2022.0011","article-title":"Antibiotic consumption and time to recovery from uncomplicated urinary tract infection: secondary analysis of observational data from a point-of-care test trial.","volume":"72","author":"Gadalla","year":"2022","journal-title":"Br J Gen Pract"},{"issue":"2","key":"zoi260926r5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0277728","article-title":"Activity impairment, health-related quality of life, productivity, and self-reported resource use and associated costs of uncomplicated urinary tract infection among women in the United States.","volume":"18","author":"Thompson","year":"2023","journal-title":"PLoS One"},{"issue":"5","key":"zoi260926r6","doi-asserted-by":"publisher","first-page":"e103","DOI":"10.1093\/cid\/ciq257","article-title":"European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.","volume":"52","author":"Gupta","year":"2011","journal-title":"Clin Infect Dis"},{"issue":"4","key":"zoi260926r7","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1007\/s11606-024-09029-6","article-title":"Risk factors for empiric treatment failure in US female outpatients with uncomplicated urinary tract infection: an observational study.","volume":"40","author":"Fromer","year":"2025","journal-title":"J Gen Intern Med"},{"key":"zoi260926r8","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jgar.2021.05.016","article-title":"Impact of inappropriate empirical antibiotic treatment on clinical outcomes of urinary tract infections caused by Escherichia coli: a retrospective cohort study.","volume":"26","author":"Zhu","year":"2021","journal-title":"J Glob Antimicrob Resist"},{"issue":"1","key":"zoi260926r9","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02359-21","article-title":"Impact of empirical antibiotic therapy on outcomes of outpatient urinary tract infection due to nonsusceptible Enterobacterales.","volume":"10","author":"Dunne","year":"2022","journal-title":"Microbiol Spectr"},{"issue":"6","key":"zoi260926r11","doi-asserted-by":"publisher","first-page":"S159","DOI":"10.1016\/j.jval.2023.03.2526","article-title":"EE548 healthcare resource use and costs associated with oral antibiotic treatment failure in uncomplicated urinary tract infection in the US.","volume":"26","author":"Franklin","year":"2023","journal-title":"Value Health"},{"issue":"6","key":"zoi260926r12","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s15010-011-0163-z","article-title":"The association of antimicrobial resistance with cure and quality of life among women with acute uncomplicated cystitis.","volume":"39","author":"Abrahamian","year":"2011","journal-title":"Infection"},{"issue":"8","key":"zoi260926r13","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1185\/030079905X56358","article-title":"Time to symptom relief for uncomplicated urinary tract infection treated with extended-release ciprofloxacin: a prospective, open-label, uncontrolled primary care study.","volume":"21","author":"Klimberg","year":"2005","journal-title":"Curr Med Res Opin"},{"issue":"609","key":"zoi260926r14","doi-asserted-by":"publisher","first-page":"e244","DOI":"10.3399\/bjgp13X665206","article-title":"Antibiotic treatment of urinary tract infection by community pharmacists: a cross-sectional study.","volume":"63","author":"Booth","year":"2013","journal-title":"Br J Gen Pract"},{"issue":"6","key":"zoi260926r15","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s10096-015-2329-6","article-title":"Quality of life and changes in symptom relief in patients with acute uncomplicated cystitis treated with antibiotics: a prospective, open-label, multicenter, observational study.","volume":"34","author":"Choi","year":"2015","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"11","key":"zoi260926r16","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1093\/cid\/ciab560","article-title":"Antimicrobial resistance trends in urine Escherichia coli isolates from adult and adolescent females in the United States from 2011 to 2019: rising ESBL strains and impact on patient management.","volume":"73","author":"Kaye","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"7309","key":"zoi260926r17","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/nature09197","article-title":"Type IIA topoisomerase inhibition by a new class of antibacterial agents.","volume":"466","author":"Bax","year":"2010","journal-title":"Nature"},{"issue":"4","key":"zoi260926r18","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1021\/acsinfecdis.8b00315","article-title":"Mechanistic and structural basis for the actions of the antibacterial gepotidacin against Staphylococcus aureus gyrase.","volume":"5","author":"Gibson","year":"2019","journal-title":"ACS Infect Dis"},{"issue":"4","key":"zoi260926r19","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1021\/acsinfecdis.3c00346","article-title":"Interactions between gepotidacin and Escherichia coli gyrase and topoisomerase IV: genetic and biochemical evidence for well-balanced dual-targeting.","volume":"10","author":"Oviatt","year":"2024","journal-title":"ACS Infect Dis"},{"issue":"4","key":"zoi260926r21","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01525-22","article-title":"Antimicrobial activity of gepotidacin tested against Escherichia coli and Staphylococcus saprophyticus isolates causing urinary tract infections in medical centers worldwide (2019 to 2020).","volume":"67","author":"Arends","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"issue":"10428","key":"zoi260926r22","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S0140-6736(23)02196-7","article-title":"Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials.","volume":"403","author":"Wagenlehner","year":"2024","journal-title":"Lancet"},{"key":"zoi260926r25","doi-asserted-by":"publisher","first-page":"r1825","DOI":"10.1136\/bmj.r1825","article-title":"Urinary tract infections: New antibiotic for women and girls is approved in UK.","volume":"390","author":"Iacobucci","year":"2025","journal-title":"BMJ"},{"issue":"20","key":"zoi260926r28","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"key":"zoi260926r10","volume-title":"Open Forum Infect Dis","author":"Franklin","year":"2023"},{"key":"zoi260926r20","author":"Mushtaq","year":"2019"},{"key":"zoi260926r23","volume-title":"ESCMID Global Abstract Book 2024","author":"Kaye","year":"2024"},{"key":"zoi260926r24","author":"US Food and Drug Administration","year":"2025"},{"key":"zoi260926r2","doi-asserted-by":"crossref","unstructured":"Trautner? BW, Cort\u00e9s-Penfield? NW, Gupta? K, Clinical practice guideline by Infectious Diseases Society of America (IDSA): 2025 guideline on management and treatment of complicated urinary tract infections: executive summary. 2025. Accessed September 10, 2025. https:\/\/www.idsociety.org\/globalassets\/idsa\/practice-guidelines\/cuti\/executive-summary.pdf","DOI":"10.1093\/cid\/ciaf462"},{"key":"zoi260926r26","unstructured":"ClinicalTrials.gov. A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (UTI). NCT04020341. Accessed July 28, 2026. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04020341"},{"key":"zoi260926r27","unstructured":"ClinicalTrials.gov. Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI). NCT04187144. Accessed July 28, 2026. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04187144"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2854615\/ramrez_2026_oi_260926_1790096170.17926.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:30:27Z","timestamp":1790695827000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2854615"}},"subtitle":["A Nonrandomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":28,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.34116","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}