{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:57:35Z","timestamp":1790740655695,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"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":[[2015,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n The unmet medical need for novel intervention strategies to treat\n Neisseria gonorrhoeae<\/jats:named-content>\n infections is significant and increasing, as rapidly emerging resistance in this pathogen is threatening to eliminate the currently available treatment options. AZD0914 is a novel bacterial gyrase inhibitor that possesses potent\n in vitro<\/jats:italic>\n activities against isolates with high-level resistance to ciprofloxacin and extended-spectrum cephalosporins, and it is currently in clinical development for the treatment of\n N. gonorrhoeae<\/jats:named-content>\n infections. The propensity to develop resistance against AZD0914 was examined in\n N. gonorrhoeae<\/jats:named-content>\n and found to be extremely low, a finding supported by similar studies with\n Staphylococcus aureus<\/jats:named-content>\n . The genetic characterization of both first-step and second-step mutants that exhibited decreased susceptibilities to AZD0914 identified substitutions in the conserved GyrB TOPRIM domain, confirming DNA gyrase as the primary target of AZD0914 and providing differentiation from fluoroquinolones. The analysis of available bacterial gyrase and topoisomerase IV structures, including those bound to fluoroquinolone and nonfluoroquinolone inhibitors, has allowed the rationalization of the lack of cross-resistance that AZD0914 shares with fluoroquinolones. Microbiological susceptibility data also indicate that the topoisomerase inhibition mechanisms are subtly different between\n N. gonorrhoeae<\/jats:named-content>\n and other bacterial species. Taken together, these data support the progression of AZD0914 as a novel treatment option for the oral treatment of\n N. gonorrhoeae<\/jats:named-content>\n infections.\n <\/jats:p>","DOI":"10.1128\/aac.04456-14","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T22:11:33Z","timestamp":1419286293000},"page":"1478-1486","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["Characterization of the Novel DNA Gyrase Inhibitor AZD0914: Low Resistance Potential and Lack of Cross-Resistance in Neisseria gonorrhoeae"],"prefix":"10.1128","volume":"59","author":[{"given":"Richard A.","family":"Alm","sequence":"first","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita D.","family":"Lahiri","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Kutschke","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda G.","family":"Otterson","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Whiteaker","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"UMass Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Huband","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humphrey","family":"Gardner","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","volume-title":"WHO: urgent action needed to prevent the spread of untreatable gonorrhoea","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. 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AZD0914, a topoisomerase inhibitor with novel MOI for treatment of infections with Neisseria gonorrhoeae, poster C-1422. 54th Annu Intersci Conf Antimicrob Agents Chemother, 5 to 9 September 2014, Washington, DC."},{"key":"e_1_3_1_22_2","volume-title":"CLSI document M07-A9","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 9th ed. CLSI document M07-A9. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"9"},{"key":"e_1_3_1_23_2","volume-title":"CLSI document M100-S23","author":"Clinical and Laboratory Standards Institute","year":"2013","unstructured":"Clinical and Laboratory Standards Institute. 2013. Performance standards for antimicrobial susceptibility testing; 23rd informational supplement. CLSI document M100-S23. 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