{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:02:05Z","timestamp":1785895325055,"version":"3.56.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"\u00d6rebro County Council Research Committee"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125\u20131 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC\u200a&gt;\u200a0.125 mg\/L), in our hollow fibre infection model (HFIM) for gonorrhoea.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Gonococcal strains examined were WHO F (ceftriaxone-susceptible, MIC\u200a&lt;\u200a0.002 mg\/L), R (ceftriaxone-resistant, MIC\u200a=\u200a0.5 mg\/L), Z (ceftriaxone-resistant, MIC\u200a=\u200a0.5 mg\/L) and X (ceftriaxone-resistant, MIC\u200a=\u200a2 mg\/L). Dose-range HFIM 7 day experiments simulating ceftriaxone 0.125\u20131 g single-dose intramuscular regimens were conducted.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Ceftriaxone 0.125\u20131 g single-dose treatments rapidly eradicated WHO F (wild-type ceftriaxone MIC). Ceftriaxone 0.5 and 1 g treatments, based on ceftriaxone human plasma pharmacokinetic parameters, eradicated most ceftriaxone-resistant gonococcal strains (WHO R and Z), but ceftriaxone 0.5 g failed to eradicate WHO X (high-level ceftriaxone resistance). When simulating oropharyngeal gonorrhoea, ceftriaxone 0.5 g failed to eradicate all the ceftriaxone-resistant strains, while ceftriaxone 1 g eradicated WHO R and Z (low-level ceftriaxone resistance) but failed to eradicate WHO X (high-level ceftriaxone resistance). No ceftriaxone-resistant mutants were selected using any ceftriaxone treatments.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Ceftriaxone 1 g single-dose intramuscularly cure most of the anogenital and oropharyngeal gonorrhoea cases caused by the currently internationally spreading ceftriaxone-resistant gonococcal strains, which should be further confirmed clinically. A ceftriaxone 1 g dose (\u00b1azithromycin 2 g) should be recommended for first-line empiric gonorrhoea treatment. This will buy countries some time until novel antimicrobials are licensed. Using ceftriaxone 1 g gonorrhoea treatment, the EUCAST ceftriaxone-resistance breakpoint is too low.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jac\/dkae063","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T20:15:08Z","timestamp":1710792908000},"page":"1006-1013","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125\u20131 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae<\/i> strains in a hollow fibre infection model for gonorrhoea"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1710-2081","authenticated-orcid":false,"given":"Magnus","family":"Unemo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, \u00d6rebro University , \u00d6rebro , Sweden"},{"name":"Institute for Global Health, University College London (UCL) , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Golparian","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, \u00d6rebro University , \u00d6rebro , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Oxelbark","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry, Department of Laboratory Medicine, Faculty of Medicine and Health, \u00d6rebro University , \u00d6rebro , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9349-3080","authenticated-orcid":false,"given":"Fabian Y S","family":"Kong","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne , Melbourne , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brown","sequence":"additional","affiliation":[{"name":"Institute for Therapeutic Innovation, College of Medicine, University of Florida , Gainesville, FL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6227-7580","authenticated-orcid":false,"given":"Arnold","family":"Louie","sequence":"additional","affiliation":[{"name":"Institute for Therapeutic Innovation, College of Medicine, University of Florida , Gainesville, FL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9162-7332","authenticated-orcid":false,"given":"George","family":"Drusano","sequence":"additional","affiliation":[{"name":"Institute for Therapeutic Innovation, College of Medicine, University of Florida , Gainesville, FL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Jacobsson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, \u00d6rebro University , \u00d6rebro , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"2024050202511329200_dkae063-B1","author":"World Health Organization (WHO)"},{"key":"2024050202511329200_dkae063-B2","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":"2024050202511329200_dkae063-B3","doi-asserted-by":"crossref","first-page":"e627","DOI":"10.1016\/S2666-5247(21)00171-3","article-title":"WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017\u201318: a retrospective observational study","volume":"2","author":"Unemo","year":"2021","journal-title":"Lancet Microbe"},{"key":"2024050202511329200_dkae063-B4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/IM9.0000000000000113","article-title":"Global transmission of the penA allele 60.001\u2013containing high-level ceftriaxone-resistant gonococcal FC428 clone and antimicrobial therapy of associated cases: a review","volume":"5","author":"van der Veen","year":"2023","journal-title":"Infect Microb Dis"},{"key":"2024050202511329200_dkae063-B5","doi-asserted-by":"crossref","first-page":"e332","DOI":"10.1016\/S1473-3099(23)00479-6","article-title":"The enhanced gonococcal surveillance programme, Cambodia","volume":"23","author":"Ouk","year":"2023","journal-title":"Lancet Infect Dis"},{"key":"2024050202511329200_dkae063-B6","article-title":"2020 European guideline for the diagnosis and treatment of gonorrhoea in adults","author":"Unemo","journal-title":"Int J STD AIDS"},{"key":"2024050202511329200_dkae063-B7","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.15585\/mmwr.mm6950a6","article-title":"Update to CDC\u2019s treatment guidelines for gonococcal infection, 2020","volume":"69","author":"St Cyr","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2024050202511329200_dkae063-B8","first-page":"332","article-title":"Update to CDC\u2019s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections","volume":"56","author":"Centers for Disease Control and Prevention (CDC)","year":"2007","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2024050202511329200_dkae063-B9","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1016\/S1473-3099(20)30171-7","article-title":"Optimising treatments for sexually transmitted infections: surveillance, pharmacokinetics and pharmacodynamics, therapeutic strategies, and molecular resistance prediction","volume":"20","author":"Se\u00f1a","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2024050202511329200_dkae063-B10","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cmi.2020.08.006","article-title":"Pharmacokinetic\/pharmacodynamic considerations for new and current therapeutic drugs for uncomplicated gonorrhoea-challenges and opportunities","volume":"26","author":"Theuretzbacher","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"2024050202511329200_dkae063-B11","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/jac\/dkq289","article-title":"Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink?","volume":"65","author":"Chisholm","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2024050202511329200_dkae063-B12","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/AAC.15.4.587","article-title":"Pharmacokinetic determinants of penicillin cure of gonococcal urethritis","volume":"15","author":"Jaffe","year":"1979","journal-title":"Antimicrob Agents Chemother"},{"key":"2024050202511329200_dkae063-B13","doi-asserted-by":"crossref","first-page":"682135","DOI":"10.3389\/fphar.2021.682135","article-title":"Pharmacodynamic evaluation of dosing, bacterial kill, and resistance suppression for zoliflodacin against Neisseria gonorrhoeae in a dynamic hollow fiber infection model","volume":"12","author":"Jacobsson","year":"2021","journal-title":"Front Pharmacol"},{"key":"2024050202511329200_dkae063-B14","doi-asserted-by":"crossref","first-page":"874176","DOI":"10.3389\/fphar.2022.874176","article-title":"Pharmacodynamic evaluation of zoliflodacin treatment of Neisseria gonorrhoeae strains with amino acid substitutions in the zoliflodacin target GyrB using a dynamic hollow fiber infection model","volume":"13","author":"Jacobsson","year":"2022","journal-title":"Front Pharmacol"},{"key":"2024050202511329200_dkae063-B15","doi-asserted-by":"crossref","first-page":"1035841","DOI":"10.3389\/fphar.2022.1035841","article-title":"Pharmacodynamic evaluation of lefamulin in the treatment of gonorrhea using a hollow fiber infection model simulating Neisseria gonorrhoeae infections","volume":"13","author":"Jacobsson","year":"2022","journal-title":"Front Pharmacol"},{"key":"2024050202511329200_dkae063-B16","doi-asserted-by":"crossref","first-page":"1291885","DOI":"10.3389\/fphar.2023.1291885","article-title":"Pharmacodynamics of zoliflodacin plus doxycycline combination therapy against Neisseria gonorrhoeae in a gonococcal hollow-fiber infection model","volume":"14","author":"Jacobsson","year":"2023","journal-title":"Front Pharmacol"},{"key":"2024050202511329200_dkae063-B17","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1093\/jac\/dkw288","article-title":"The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization","volume":"71","author":"Unemo","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2024050202511329200_dkae063-B18","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1128\/AAC.00504-16","article-title":"New ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain with a novel mosaic penA gene isolated in Japan","volume":"60","author":"Nakayama","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"2024050202511329200_dkae063-B19","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1093\/jac\/dkz376","article-title":"In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae","volume":"74","author":"Foerster","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2024050202511329200_dkae063-B20"},{"key":"2024050202511329200_dkae063-B21","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1136\/sextrans-2016-052950","article-title":"Neisseria gonorrhoeae DNA bacterial load in men with symptomatic and asymptomatic gonococcal urethritis","volume":"93","author":"Priest","year":"2017","journal-title":"Sex Transm Infect"},{"key":"2024050202511329200_dkae063-B22","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1128\/JCM.01186-16","article-title":"Neisseria gonorrhoeae bacterial DNA load in the pharynges and saliva of men who have sex with men","volume":"54","author":"Chow","year":"2016","journal-title":"J Clin Microbiol"},{"key":"2024050202511329200_dkae063-B23","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1128\/JCM.05341-11","article-title":"Differing Neisseria gonorrhoeae bacterial loads in the pharynx and rectum in men who have sex with men: implications for gonococcal detection, transmission, and control","volume":"49","author":"Bissessor","year":"2011","journal-title":"J Clin Microbiol"},{"key":"2024050202511329200_dkae063-B24","author":"Roche"},{"key":"2024050202511329200_dkae063-B25","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1159\/000238415","article-title":"Human pharmacokinetics and distribution in various tissues of ceftriaxone","volume":"32","author":"Fraschini","year":"1986","journal-title":"Chemotherapy"},{"key":"2024050202511329200_dkae063-B26","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1542\/peds.2004-2294","article-title":"Explaining the poor bacteriologic eradication rate of single-dose ceftriaxone in group a streptococcal tonsillopharyngitis: a reverse engineering solution using pharmacodynamic modeling","volume":"116","author":"Blumer","year":"2005","journal-title":"Pediatrics"},{"key":"2024050202511329200_dkae063-B27","doi-asserted-by":"crossref","first-page":"2300456","DOI":"10.2807\/1560-7917.ES.2023.28.37.2300456","article-title":"Two cases of extensively drug-resistant (XDR) Neisseria gonorrhoeae infection combining ceftriaxone-resistance and high-level azithromycin resistance, France, November 2022 and May 2023","volume":"28","author":"Maubaret","year":"2023","journal-title":"Euro Surveill"},{"key":"2024050202511329200_dkae063-B28","doi-asserted-by":"crossref","first-page":"2300125","DOI":"10.2807\/1560-7917.ES.2023.28.10.2300125","article-title":"Multidrug-resistant Neisseria gonorrhoeae isolate SE690: mosaic penA-60.001 gene causing ceftriaxone resistance internationally has spread to the more antimicrobial-susceptible genomic lineage, Sweden, September 2022","volume":"28","author":"Golparian","year":"2023","journal-title":"Euro Surveill"},{"key":"2024050202511329200_dkae063-B29","doi-asserted-by":"crossref","first-page":"2200899","DOI":"10.2807\/1560-7917.ES.2022.27.50.2200899","article-title":"Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 2022","volume":"27","author":"Ber\u00e7ot","year":"2022","journal-title":"Euro Surveill"},{"key":"2024050202511329200_dkae063-B30","doi-asserted-by":"crossref","first-page":"2200803","DOI":"10.2807\/1560-7917.ES.2022.27.46.2200803","article-title":"Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022","volume":"27","author":"Day","year":"2022","journal-title":"Euro Surveill"},{"key":"2024050202511329200_dkae063-B31","doi-asserted-by":"crossref","first-page":"2200455","DOI":"10.2807\/1560-7917.ES.2022.27.24.2200455","article-title":"Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022","volume":"27","author":"Pleininger","year":"2022","journal-title":"Euro Surveill"},{"key":"2024050202511329200_dkae063-B32","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1093\/jac\/dkz129","article-title":"Clonal expansion and spread of the ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, identified in Japan in 2015, and closely related isolates","volume":"74","author":"Lee","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2024050202511329200_dkae063-B33","doi-asserted-by":"crossref","first-page":"e452","DOI":"10.1016\/S2666-5247(22)00044-1","article-title":"Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study","volume":"3","author":"S\u00e1nchez-Bus\u00f3","year":"2022","journal-title":"Lancet Microbe"},{"key":"2024050202511329200_dkae063-B34","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1136\/sti.2010.042317","article-title":"Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 east European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial","volume":"86","author":"Unemo","year":"2010","journal-title":"Sex Transm Infect"},{"key":"2024050202511329200_dkae063-B35","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\u20132018","volume":"127","author":"Boiko","year":"2019","journal-title":"APMIS"},{"key":"2024050202511329200_dkae063-B36","doi-asserted-by":"crossref","first-page":"e02069","DOI":"10.1128\/AAC.02069-17","article-title":"Neisseria cinerea with high ceftriaxone MIC is a source of ceftriaxone and cefixime resistance-mediating penA sequences in Neisseria gonorrhoeae","volume":"62","author":"Igawa","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2024050202511329200_dkae063-B37","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/jac\/dky548","article-title":"Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review","volume":"74","author":"Kong","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2024050202511329200_dkae063-B38","doi-asserted-by":"crossref","first-page":"e01644","DOI":"10.1128\/AAC.01644-18","article-title":"Pharmacokinetic data are predictive of in vivo efficacy for cefixime and ceftriaxone against susceptible and resistant Neisseria gonorrhoeae strains in the gonorrhea mouse model","volume":"63","author":"Connolly","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2024050202511329200_dkae063-B39","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/jac\/dkac366","article-title":"GyrB in silico mining in 27 151 global gonococcal genomes from 1928\u20132021 combined with zoliflodacin in vitro testing of 71 international gonococcal isolates with different GyrB, ParC and ParE substitutions confirms high susceptibility","volume":"78","author":"Golparian","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2024050202511329200_dkae063-B40","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1056\/NEJMoa1706988","article-title":"Single-Dose zoliflodacin (ETX0914) for treatment of urogenital gonorrhea","volume":"379","author":"Taylor","year":"2018","journal-title":"N Engl J Med"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/5\/1006\/57368070\/dkae063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/5\/1006\/57368070\/dkae063.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T02:51:42Z","timestamp":1714618302000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/79\/5\/1006\/7630705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3,18]]},"published-print":{"date-parts":[[2024,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae063","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2024,3,18]]}}}