{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T14:29:19Z","timestamp":1789223359269,"version":"build-2803163510"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T00:00:00Z","timestamp":1595721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"\u00d6rebro County Council Research Committee"},{"DOI":"10.13039\/501100002915","name":"Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006736","name":"\u00d6rebro University Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006736","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Summit Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The rising incidence of antimicrobial resistance in Neisseria gonorrhoeae may result in untreatable gonorrhoea in certain circumstances and development of novel antimicrobials is urgently needed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, DIS-73285, against a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates and reference strains, including various types of high-level resistant, MDR and XDR gonococcal isolates (n\u2009=\u2009262).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MICs (mg\/L) of DIS-73285 were determined by agar dilution and by Etest for ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>DIS-73285 was substantially more potent than any of the currently or previously used therapeutic antimicrobials, with MICs ranging from \u22640.001 to 0.004\u2009mg\/L, and the MIC50, MIC90 and modal MIC all \u22640.001\u2009mg\/L (lowest MIC tested). No correlation with the MICs of DIS-73285 and the MICs of any of the currently or previously used antimicrobials was observed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The novel chemotype, small-molecule antimicrobial DIS-73285, demonstrated high in vitro potency against all tested N. gonorrhoeae isolates. Further in vitro and in vivo studies, evaluating efficacy, resistance emergence, pharmacokinetic\/pharmacodynamic parameters, toxicity and safety, should be conducted to evaluate DIS-73285 as a therapy specifically for urogenital and extra-genital gonorrhoea.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa322","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T19:11:05Z","timestamp":1593630665000},"page":"3244-3247","source":"Crossref","is-referenced-by-count":7,"title":["High in vitro activity of DIS-73285, a novel antimicrobial with a new mechanism of action, against MDR and XDR Neisseria gonorrhoeae"],"prefix":"10.1093","volume":"75","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":"Clive","family":"Mason","sequence":"additional","affiliation":[{"name":"Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawaz","family":"Khan","sequence":"additional","affiliation":[{"name":"Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Meo","sequence":"additional","affiliation":[{"name":"Summit Therapeutics, Merrifield Centre, Rosemary Lane, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1710-2081","authenticated-orcid":false,"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":[[2020,7,26]]},"reference":[{"key":"2020101604545468800_dkaa322-B1","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/CMR.00010-14","article-title":"Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future","volume":"27","author":"Unemo","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"2020101604545468800_dkaa322-B2","doi-asserted-by":"crossref","first-page":"e1002344","DOI":"10.1371\/journal.pmed.1002344","article-title":"Antimicrobial resistance in Neisseria gonorrhoeae: global surveillance and a call for international collaborative action","volume":"14","author":"Wi","year":"2017","journal-title":"PLoS Med"},{"key":"2020101604545468800_dkaa322-B3","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1071\/SH19023","article-title":"World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts","volume":"16","author":"Unemo","year":"2019","journal-title":"Sex Health"},{"key":"2020101604545468800_dkaa322-B4","year":"2016"},{"key":"2020101604545468800_dkaa322-B5","first-page":"1","article-title":"Sexually transmitted diseases treatment guidelines, 2015","volume":"64","author":"Workowski","year":"2015","journal-title":"MMWR Recomm Rep"},{"key":"2020101604545468800_dkaa322-B6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/0956462412472837","article-title":"European guideline on the diagnosis and treatment of gonorrhoea in adults","volume":"24","author":"Bignell","year":"2012","journal-title":"Int J STD AIDS"},{"key":"2020101604545468800_dkaa322-B7","author":"Romanowski","year":"2013"},{"key":"2020101604545468800_dkaa322-B8","year":"2016"},{"key":"2020101604545468800_dkaa322-B9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/0956462419886775","article-title":"2018 UK national guideline for the management of infection with Neisseria gonorrhoeae","volume":"31","author":"Fifer","year":"2020","journal-title":"Int J STD AIDS"},{"key":"2020101604545468800_dkaa322-B10","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/apm.12948","article-title":"Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018","volume":"127","author":"Boiko","year":"2019","journal-title":"APMIS"},{"key":"2020101604545468800_dkaa322-B11","first-page":"52","article-title":"Gonococcal infection. 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