{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:35:06Z","timestamp":1785825306202,"version":"3.56.0"},"reference-count":40,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"unspecified","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["APP1181057"],"award-info":[{"award-number":["APP1181057"]}]},{"name":"Australian National Health and Medical Research Council","award":["APP2007007"],"award-info":[{"award-number":["APP2007007"]}]},{"name":"Australian National Health and Medical Research Council","award":["APP2009736"],"award-info":[{"award-number":["APP2009736"]}]},{"name":"Australian National Health and Medical Research Council","award":["GNT1172873"],"award-info":[{"award-number":["GNT1172873"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,10,18]]},"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                      infections are common and incidence increasing. Oropharyngeal infections are associated with greater treatment failure compared with other sites and drive transmission to anogenital sites through saliva. Gonococcal resistance is increasing and new treatments are scarce, therefore, clinicians must optimise currently available and emerging treatments in order to have efficacious therapeutic options. This requires pharmacokinetic data from the oral cavity\/oropharynx, however, availability of such information is currently limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Healthy male volunteers (participants) recruited into the study will receive single doses of either ceftriaxone 1\u2009g, cefixime 400\u2009mg or ceftriaxone 500\u2009mg plus 2\u2009g azithromycin. Participants will provide samples at 6-8 time points (treatment regimen dependent) from four oral sites, two oral fluids, one anorectal swab and blood. Participants will complete online questionnaires about their medical history, sexual practices and any side effects experienced up to days 5\u20137. Saliva\/oral mucosal pH and oral microbiome analysis will be undertaken. Bioanalysis will be conducted by liquid chromatography-mass spectrometry. Drug concentrations over time will be used to develop mathematical models for optimisation of drug dosing regimens and to estimate pharmacodynamic targets of efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study was approved by Royal Melbourne Hospital Human Research Ethics Committee (60370\/MH-2021). The study results will be submitted for publication in peer-reviewed journals and reported at conferences. Summary results will be sent to participants requesting them. All data relevant to the study will be included in the article or uploaded as supplementary information.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ACTRN12621000339853.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-064782","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T10:08:34Z","timestamp":1668161314000},"page":"e064782","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Optimisation of treatments for oral\n                    <i>Neisseria gonorrhoeae<\/i>\n                    infection: Pharmacokinetics Study (STI-PK project) \u2013 study protocol for non-randomised clinical trial"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9349-3080","authenticated-orcid":false,"given":"Fabian Y S","family":"Kong","sequence":"first","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Unemo","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, \u00d6rebro University, Orebro, Sweden"},{"name":"Institute for Global Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shueh H","family":"Lim","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"The Crane General Practice, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngaire","family":"Latch","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia"},{"name":"Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A","family":"Roberts","sequence":"additional","affiliation":[{"name":"The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia"},{"name":"Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia"},{"name":"Herston Infectious Diseases Institute, Metro North Health, Brisbane, Queensland, Australia"},{"name":"Division of Anaesthesiology Critical Care Emergency and Pain Medicine, N\u00eemes University Hospital, University of Montpellier, N\u00eemes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C","family":"Wallis","sequence":"additional","affiliation":[{"name":"The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L","family":"Parker","sequence":"additional","affiliation":[{"name":"The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia B","family":"Landersdorfer","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"Yap","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K","family":"Fairley","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia"},{"name":"Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P F","family":"Chow","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia"},{"name":"Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Lewis","sequence":"additional","affiliation":[{"name":"Westmead Clinical School and Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane S","family":"Hocking","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"2025121220565127000_12.11.e064782.1","unstructured":"World Health Organisation . actions for impact. In: Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. accountability for the global health sector strategies 2016\u20132021, 2021."},{"key":"2025121220565127000_12.11.e064782.2","unstructured":"National Notifiable Diseases Surveillance System . Number of notifications of gonococcal infections, Australia, by age group and sex, 2021."},{"key":"2025121220565127000_12.11.e064782.3","unstructured":"Centers for Disease Control and Prevention . Sexually Transmitted Disease Surveillance 2017 report. In: Atlanta: U.S : Department of Health and Human Services, 2017."},{"key":"2025121220565127000_12.11.e064782.4","unstructured":"Public Health England (PHE) . Sexually transmitted infections and screening for Chlamydia in England, 2018. 13, 2019."},{"key":"2025121220565127000_12.11.e064782.5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/5758387","article-title":"Extragenital infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae: a review of the literature","volume":"2016","author":"Chan","year":"2016","journal-title":"Infect Dis Obstet Gynecol"},{"key":"2025121220565127000_12.11.e064782.6","doi-asserted-by":"publisher","DOI":"10.1097\/00007435-199501000-00007"},{"key":"2025121220565127000_12.11.e064782.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30304-4"},{"key":"2025121220565127000_12.11.e064782.8","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00010-14"},{"key":"2025121220565127000_12.11.e064782.9","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 2017-18: a retrospective observational study","volume":"2","author":"Unemo","year":"2021","journal-title":"Lancet Microbe"},{"key":"2025121220565127000_12.11.e064782.10","unstructured":"World Health Organisation . Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. Geneva, Switzerland: WHO, 2017."},{"key":"2025121220565127000_12.11.e064782.11","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky548"},{"key":"2025121220565127000_12.11.e064782.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002366"},{"key":"2025121220565127000_12.11.e064782.13","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa300"},{"key":"2025121220565127000_12.11.e064782.14","doi-asserted-by":"publisher","DOI":"10.1177\/0956462419886775"},{"key":"2025121220565127000_12.11.e064782.15","unstructured":"Australian Sexual Health Alliance . Australian STI management guidelines for use in primary care, 2021."},{"key":"2025121220565127000_12.11.e064782.16","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6404a1"},{"key":"2025121220565127000_12.11.e064782.17","unstructured":"World Health Organisation . Who guidelines for the treatment of Neisseria gonorrhoeae, 2016."},{"key":"2025121220565127000_12.11.e064782.18","first-page":"095646242094912","article-title":"2020 European guideline for the diagnosis and treatment of gonorrhoea in adults","volume":"2020","author":"Unemo","year":"2020","journal-title":"Int J STD AIDS"},{"key":"2025121220565127000_12.11.e064782.19","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.jpba.2017.10.023","article-title":"A UHPLC-MS\/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent","volume":"148","author":"Naicker","year":"2018","journal-title":"J Pharm Biomed Anal"},{"key":"2025121220565127000_12.11.e064782.20","doi-asserted-by":"publisher","DOI":"10.1080\/000155501750376258"},{"key":"2025121220565127000_12.11.e064782.21","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/OLQ.0000000000000844","article-title":"A phase 1 pharmacokinetic and safety study of Extended-Duration, high-dose cefixime for cephalosporin-resistant Neisseria gonorrhoeae in the pharynx","volume":"45","author":"Barbee","year":"2018","journal-title":"Sex Transm Dis"},{"key":"2025121220565127000_12.11.e064782.22","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-012-9280-2"},{"key":"2025121220565127000_12.11.e064782.23","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200948020-00002"},{"key":"2025121220565127000_12.11.e064782.24","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41586-021-03891-8","article-title":"Bioaccumulation of therapeutic drugs by human gut bacteria","volume":"597","author":"Kl\u00fcnemann","year":"2021","journal-title":"Nature"},{"key":"2025121220565127000_12.11.e064782.25","doi-asserted-by":"crossref","first-page":"e01757","DOI":"10.1128\/spectrum.01757-21","article-title":"The impact of mouthwash on the oropharyngeal microbiota of men who have sex with men: a substudy of the omega trial","volume":"10","author":"Plummer","year":"2022","journal-title":"Microbiol Spectr"},{"key":"2025121220565127000_12.11.e064782.26","doi-asserted-by":"crossref","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":"2025121220565127000_12.11.e064782.27","doi-asserted-by":"crossref","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":"2025121220565127000_12.11.e064782.28","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2015-052502"},{"key":"2025121220565127000_12.11.e064782.29","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2018-053950"},{"key":"2025121220565127000_12.11.e064782.30","unstructured":"World Health Organisation . Antimicrobial resistance: global report on surveillance, 2014."},{"key":"2025121220565127000_12.11.e064782.31","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm476"},{"key":"2025121220565127000_12.11.e064782.32","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.841-851.2006"},{"key":"2025121220565127000_12.11.e064782.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174372"},{"key":"2025121220565127000_12.11.e064782.34","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/jac\/dkx392","article-title":"Chlamydia trachomatis antimicrobial susceptibility in colorectal and endocervical cells","volume":"73","author":"Foschi","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2025121220565127000_12.11.e064782.35","first-page":"449","article-title":"Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea: the relationship between antibiotic MIC and clinical outcome","volume":"75","author":"Cole","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2025121220565127000_12.11.e064782.36","doi-asserted-by":"publisher","DOI":"10.1086\/510079"},{"key":"2025121220565127000_12.11.e064782.37","doi-asserted-by":"publisher","DOI":"10.1086\/511422"},{"key":"2025121220565127000_12.11.e064782.38","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.15.4.587"},{"key":"2025121220565127000_12.11.e064782.39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4103\/JPBS.JPBS_56_19","article-title":"Gingival crevicular fluid: an overview","volume":"11","author":"Subbarao","year":"2019","journal-title":"J Pharm Bioallied Sci"},{"key":"2025121220565127000_12.11.e064782.40","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510368650"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-064782","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T04:56:59Z","timestamp":1765601819000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-064782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11,11]]},"published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1136\/bmjopen-2022-064782"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-064782","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11]]}}}