{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T14:29:16Z","timestamp":1789223356995,"version":"build-2803163510"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria gonorrhoeae<\/jats:named-content>\n            against all antimicrobials available for the treatment of gonorrhea has emerged. The first gonococcal strains with high-level resistance to ceftriaxone, the last option for first-line empirical antimicrobial monotherapy, were recently described. Consequently, new treatment options are essential. In this study, the\n            <jats:italic>in vitro<\/jats:italic>\n            activity of the novel spiropyrimidinetrione ETX0914 (AZD0914), a DNA topoisomerase II inhibitor, was investigated among contemporary consecutive clinical\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. gonorrhoeae<\/jats:named-content>\n            isolates obtained in 21 European countries and compared to the activities of antimicrobials currently or previously recommended for treatment. Consecutive clinical\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. gonorrhoeae<\/jats:named-content>\n            isolates (\n            <jats:italic>n<\/jats:italic>\n            = 873) cultured in 21 European countries from 2012 to 2014 were examined for their susceptibility to ETX0914. The MICs of ETX0914 were determined using the agar dilution method. For comparison, the MICs of ceftriaxone, cefixime, azithromycin, and ciprofloxacin were determined using Etest or the agar dilution method. For ETX0914, the MIC range, modal MIC, MIC\n            <jats:sub>50<\/jats:sub>\n            , and MIC\n            <jats:sub>90<\/jats:sub>\n            were \u22640.002 to 0.25 mg\/liter, 0.125 mg\/liter, 0.064 mg\/liter, and 0.125 mg\/liter, respectively. The MIC values were substantially lower than those of the fluoroquinolone ciprofloxacin and most other antimicrobials examined. No cross-resistance with any other examined antimicrobial was observed. In conclusion, the\n            <jats:italic>in vitro<\/jats:italic>\n            susceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical isolates from 21 European countries was high, and no cross-resistance to antimicrobials currently or previously used for gonorrhea treatment was indicated. Additional studies investigating the\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            induction and mechanisms of ETX0914 resistance in gonococci, pharmacokinetics\/pharmacodynamics in modeling\/simulations and in humans, and performance in randomized controlled gonorrhea treatment trials are essential.\n          <\/jats:p>","DOI":"10.1128\/aac.00786-15","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T03:01:14Z","timestamp":1434423674000},"page":"5220-5225","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["High\n            <i>In Vitro<\/i>\n            Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 2014"],"prefix":"10.1128","volume":"59","author":[{"given":"Magnus","family":"Unemo","sequence":"first","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Ringlander","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Wiggins","sequence":"additional","affiliation":[{"name":"Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Fredlund","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Jacobsson","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Cole","sequence":"additional","affiliation":[{"name":"Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Global incidence and prevalence of selected curable sexually transmitted infections\u20132008","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. Global incidence and prevalence of selected curable sexually transmitted infections\u20132008. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/reproductivehealth\/publications\/rtis\/2008_STI_estimates.pdf. Accessed 31 March 2015."},{"key":"e_1_3_2_3_2","volume-title":"Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. World Health Organization, Department of Reproductive Health and Research, Geneva, Switzerland. http:\/\/whqlibdoc.who.int\/publications\/2012\/9789241503501_eng.pdf. 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Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010. Euro Surveill 16(6):pii=19792. http:\/\/www.eurosurveillance.org\/ViewArticle.aspx?ArticleId=19792.","journal-title":"Euro Surveill"},{"issue":"25","key":"e_1_3_2_16_2","doi-asserted-by":"crossref","DOI":"10.2807\/ese.17.25.20200-en","article-title":"Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011","volume":"17","author":"Unemo M","year":"2012","unstructured":"Unemo M, Golparian D, Poto\u010dnik M, Jeverica S. 2012. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. 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Euro Surveill 19(30):pii=20862. http:\/\/www.eurosurveillance.org\/ViewArticle.aspx?ArticleId=20862.","journal-title":"Euro Surveill"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04124-14"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr4003984"},{"key":"e_1_3_2_22_2","volume-title":"Abstr 54th Intersci Conf Antimicrob Agents Chemother","author":"Palmer T","year":"2014","unstructured":"Palmer T, Walkup G, Basarab G, Fan J, Mills SD, Shapiro A, Sriram S, Andrews B, Gao N, Thresher J, deJonge B, Kem G. 2014. AZD0914: a Neisseria gonorrhoeae topoisomerase II inhibitor with novel mode of inhibition, poster C-1422. Abstr 54th Intersci Conf Antimicrob Agents Chemother. 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Safety and pharmacokinetics of single escalating oral doses of AZD0914: a novel spiropyrimidinetrione antibacterial agent, poster F-267. Abstr 54th Intersci Conf Antimicrob Agents Chemother. 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