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High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018

2021-04-13Journal article Restricted access
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dc.contributor.authorUnemo, Magnus
dc.contributor.authorAhlstrand, Josefine
dc.contributor.authorSánchez-Busó, Leonor
dc.contributor.authorDay, Michaela
dc.contributor.authorAanensen, David
dc.contributor.authorGolparian, Daniel
dc.contributor.authorJacobsson, Susanne
dc.contributor.authorCole, Michelle J.
dc.contributor.authorEuropean Collaborative Group
dc.date.accessioned2022-02-01T15:28:12Z
dc.date.available2022-02-01T15:28:12Z
dc.date.issued2021-04-13
dc.descriptionRandomized Controlled Trialpt_PT
dc.descriptionEuropean Collaborative Group: Raquel Abad Torreblanca, Lena Rós Ásmundsdóttir, Eszter Balla, Irith De Baetselier, Beatrice Bercot, Anna Carannante, Dominique Caugant, Maria José Borrego, Susanne Buder, Robert Cassar, Michelle Cole, Alje van Dam, Claudia Eder, Steen Hoffmann, Blazenka Hunjak, Samo Jeverica, Vesa Kirjavainen, Panayiota Maikanti-Charalambous, Vivi Miriagou, Beata Mlynarczyk-Bonikowska, Gatis Pakarna, Lynsey Patterson, Peter Pavlik, Monique Perrin, Jill Shepherd, Paola Stefanelli, Magnus Unemo, Jelena Viktorova, Hana Zákouckápt_PT
dc.descriptionEuropean Collaborative Group: Portugal - Maria José Borrego, INSA.pt_PT
dc.description.abstractObjectives: Novel antimicrobials for treatment of gonorrhoea are imperative. The first-in-class spiropyrimidinetrione zoliflodacin is promising and currently in an international Phase 3 randomized controlled clinical trial (RCT) for treatment of uncomplicated gonorrhoea. We evaluated the in vitro activity of and the genetic conservation of the target (GyrB) and other potential zoliflodacin resistance determinants among 1209 consecutive clinical Neisseria gonorrhoeae isolates obtained from 25 EU/European Economic Area (EEA) countries in 2018 and compared the activity of zoliflodacin with that of therapeutic antimicrobials currently used. Methods: MICs of zoliflodacin, ceftriaxone, cefixime, azithromycin and ciprofloxacin were determined using an agar dilution technique for zoliflodacin or using MIC gradient strip tests or an agar dilution technique for the other antimicrobials. Genome sequences were available for 96.1% of isolates. Results: Zoliflodacin modal MIC, MIC50, MIC90 and MIC range were 0.125, 0.125, 0.125 and ≤0.004-0.5 mg/L, respectively. The resistance was 49.9%, 6.7%, 1.6% and 0.2% to ciprofloxacin, azithromycin, cefixime and ceftriaxone, respectively. Zoliflodacin did not show any cross-resistance to other tested antimicrobials. GyrB was highly conserved and no zoliflodacin gyrB resistance mutations were found. No fluoroquinolone target GyrA or ParC resistance mutations or mutations causing overexpression of the MtrCDE efflux pump substantially affected the MICs of zoliflodacin. Conclusions: The in vitro susceptibility to zoliflodacin was high and the zoliflodacin target GyrB was conserved among EU/EEA gonococcal isolates in 2018. This study supports further clinical development of zoliflodacin. However, additional zoliflodacin data regarding particularly the treatment of pharyngeal gonorrhoea, pharmacokinetics/pharmacodynamics and resistance selection, including suppression, would be valuable.pt_PT
dc.description.sponsorshipThe present work was funded by grants from the O¨rebro County Council Research Committee and the Foundation for Medical Research at O¨rebro University Hospital, Sweden. Work at the WHO Collaborating Centre for Gonorrhoea and Other STIs is additionally supported by grants to M.U. from the WHO and the Global Antibiotic Research and Development Partnership (GARDP). L.S.-B. was supported by the Li Ka Shing Foundation (Big Data Institute, University of Oxford, UK) and the Centre for Genomic Pathogen Surveillance (CGPS; http://pathogensurveillance.net) when this work was conceived. Currently, L.S.-B. is funded by Plan GenT (CDEI-06/ 20-B), Conselleria de Sanitat Universal i Salut Pu´blica, Generalitat Valenciana, Valencia, Spain.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Antimicrob Chemother. 2021 Apr 13;76(5):1221-1228. doi: 10.1093/jac/dkab024pt_PT
dc.identifier.doi10.1093/jac/dkab024pt_PT
dc.identifier.issn0305-7453
dc.identifier.urihttp://hdl.handle.net/10400.18/7902
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Press/ British Society for Antimicrobial Chemotherapypt_PT
dc.relation.publisherversionhttps://academic.oup.com/jac/article-abstract/76/5/1221/6132079?redirectedFrom=fulltext&login=falsept_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nd/4.0/pt_PT
dc.subjectMutationpt_PT
dc.subjectGonococcal Infectionpt_PT
dc.subjectNeisseria Gonorrhoeaept_PT
dc.subjectAntimicrobialspt_PT
dc.subjectZoliflodacinpt_PT
dc.subjectEuropept_PT
dc.subjectInfecções Gastrointestinaispt_PT
dc.titleHigh susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1228pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage1221pt_PT
oaire.citation.titleJournal of Antimicrobial Chemotherapypt_PT
oaire.citation.volume76pt_PT
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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