{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:13:55Z","timestamp":1791422035151,"version":"4.3.3"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Gepotidacin (formerly GSK2140944) is a novel, first-in-class, triazaacenaphthylene antibacterial that inhibits bacterial DNA gyrase and topoisomerase IV via a unique mechanism and has demonstrated\n            <jats:italic>in vitro<\/jats:italic>\n            activity against\n            <jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>\n            , including drug-resistant strains, and also targets pathogens associated with other conventional and biothreat infections. Broth microdilution was used to evaluate the MIC and minimum bactericidal concentration (MBC) activity of gepotidacin and comparators against 25\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            strains (including five ciprofloxacin-nonsusceptible strains). Gepotidacin activity was also evaluated against three\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            strains (including a ciprofloxacin-nonsusceptible strain) for resistance development, against three\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            strains (including two tetracycline- and azithromycin-nonsusceptible strains) using time-kill kinetics and checkerboard methods, and against two\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            strains for the investigation of postantibiotic (PAE) and subinhibitory (PAE-SME) effects. The MIC\n            <jats:sub>50<\/jats:sub>\n            and MIC\n            <jats:sub>90<\/jats:sub>\n            for gepotidacin against the 25\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            isolates tested were 0.12 and 0.25 \u03bcg\/ml, respectively. The MBC\n            <jats:sub>50<\/jats:sub>\n            and MBC\n            <jats:sub>90<\/jats:sub>\n            for gepotidacin were 0.25 and 0.5 \u03bcg\/ml, respectively. Gepotidacin was bactericidal, and single-step resistance selection studies did not recover any mutants, indicating a low rate of spontaneous single-step resistance. For combinations of gepotidacin and comparators tested using checkerboard methods, there were no instances where antagonism occurred and only one instance of synergy (with moxifloxacin; fractional inhibitory concentration, 0.375). This was not confirmed by\n            <jats:italic>in vitro<\/jats:italic>\n            time-kill studies. The PAE for gepotidacin against the wild-type strain ranged from 0.5 to &gt;2.5 h, and the PAE-SME was &gt;2.5 h. These\n            <jats:italic>in vitro<\/jats:italic>\n            data indicate that further study of gepotidacin is warranted for potential use in treating infections caused by\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.02047-16","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T02:30:27Z","timestamp":1484015427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["<i>In Vitro<\/i>\n            Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae"],"prefix":"10.1128","volume":"61","author":[{"given":"D. J.","family":"Farrell","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. S.","family":"Sader","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Rhomberg","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. E.","family":"Scangarella-Oman","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. K.","family":"Flamm","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"2013 sexually transmitted disease surveillance","author":"Centers for Disease Control and Prevention","year":"2014","unstructured":"Centers for Disease Control and Prevention. 2014. 2013 sexually transmitted disease surveillance. Centers for Disease Control and Prevention,Atlanta, GA."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/sti.75.1.3"},{"key":"e_1_3_2_4_2","first-page":"332","article-title":"Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections","volume":"56","author":"Centers for Disease Control and Prevention","year":"2007","unstructured":"Centers for Disease Control and Prevention. 2007. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep56:332\u2013336.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.176575"},{"key":"e_1_3_2_6_2","first-page":"590","article-title":"Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections","volume":"61","author":"Centers for Disease Control and Prevention","year":"2012","unstructured":"Centers for Disease Control and Prevention. 2012. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep61:590\u2013594.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02608-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02820-15"},{"key":"e_1_3_2_10_2","volume-title":"M07-A10: methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. M07-A10: methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard,10th ed. Clinical and Laboratory Standards Institute,Wayne, PA.","edition":"10"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00527-16"},{"key":"e_1_3_2_12_2","volume-title":"Performance standards for antimicrobial susceptibility testing: 26th informational supplement","author":"Clinical and Laboratory Standards Institute","year":"2016","unstructured":"Clinical and Laboratory Standards Institute. 2016. M100-S26. Performance standards for antimicrobial susceptibility testing: 26th informational supplement. Clinical and Laboratory Standards Institute,Wayne, PA."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00496-08"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00571-15"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04077-14"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02778-13"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/48.4.545"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku073"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.9.4321-4327.2005"},{"key":"e_1_3_2_20_2","volume-title":"M26-A: methods for determining bactericidal activity of antimicrobial agents; approved guideline","author":"Clinical and Laboratory Standards Institute","year":"1999","unstructured":"Clinical and Laboratory Standards Institute. 1999. M26-A: methods for determining bactericidal activity of antimicrobial agents; approved guideline. Clinical and Laboratory Standards Institute,Wayne, PA."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818814.ch5.16"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"5.14.2.1","DOI":"10.1128\/9781555818814","volume-title":"Clinical microbiology procedures handbook","author":"Leber AL","year":"2016","unstructured":"Leber AL (ed). 2016. Antimicrobial susceptibility testing, p. 5.14.2.1\u20135.14.2.12. Clinical microbiology procedures handbook,4th ed. ASM Press,Washington, DC.","edition":"4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/31.6.881"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.9.1852"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.1253"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02047-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02047-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:45:59Z","timestamp":1645476359000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02047-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1128\/AAC.02047-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.02047-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3]]},"assertion":[{"value":"2016-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02047-16"}}