{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:14:02Z","timestamp":1791422042324,"version":"4.3.3"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T00:00:00Z","timestamp":1527033600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Increased antimicrobial resistance surveillance and new effective antimicrobials are crucial to maintain treatable gonorrhoea. We examined the in vitro activity of gepotidacin, a novel triazaacenaphthylene, and the effect of efflux pump inactivation on clinical Neisseria gonorrhoeae isolates and international reference strains (n\u2009=\u2009252) and compared gepotidacin with antimicrobials currently or previously recommended for gonorrhoea treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MICs (mg\/L) were determined by agar dilution (gepotidacin) or by Etest (seven other antimicrobials). The gyrA and parC genes were sequenced and the impact of inactivation of the MtrCDE, MacAB and NorM efflux pumps on gepotidacin MICs was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gepotidacin showed potent in vitro activity against all gonococcal isolates (n\u2009=\u2009252; MIC \u22644\u2009mg\/L). The modal MIC, MIC50, MIC90 and MIC range of gepotidacin were 0.5, 0.5, 1 and 0.032\u20134\u2009mg\/L, respectively. Inactivation of the MtrCDE efflux pump, but not MacAB or NorM, decreased the gepotidacin MICs for most strains. No significant cross-resistance between gepotidacin and any other antimicrobials, including the fluoroquinolone ciprofloxacin, was identified. However, the ParC D86N mutation (possibly together with additional antimicrobial resistance mutation), which is associated with fluoroquinolone resistance, was associated with increased gepotidacin MICs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gepotidacin demonstrated high in vitro activity against gonococcal strains, indicating that gepotidacin could potentially be an effective option for gonorrhoea treatment, particularly in a dual antimicrobial therapy regimen and for patients with resistance or allergy to extended-spectrum cephalosporins. Nevertheless, elucidating in vitro and in vivo resistance emergence and mechanisms in detail, together with further gonorrhoea clinical studies, ideally also including chlamydia and Mycoplasma genitalium are essential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dky162","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T15:10:52Z","timestamp":1523632252000},"page":"2072-2077","source":"Crossref","is-referenced-by-count":82,"title":["In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae"],"prefix":"10.1093","volume":"73","author":[{"given":"Susanne","family":"Jacobsson","sequence":"first","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Golparian","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Scangarella-Oman","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Unemo","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,22]]},"reference":[{"key":"2019120300405232700_dky162-B1","doi-asserted-by":"crossref","first-page":"e0143304.","DOI":"10.1371\/journal.pone.0143304","article-title":"Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting","volume":"10","author":"Newman","year":"2015","journal-title":"PLoS One"},{"key":"2019120300405232700_dky162-B2","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 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