{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:46:15Z","timestamp":1790739975181,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The development of new gonorrhoea treatment guidelines typically considers the resistance-inducing effect of the treatment only on Neisseria gonorrhoeae. Antimicrobial resistance in N. gonorrhoeae has, however, frequently first emerged in commensal Neisseria species and then been passed on to N. gonorrhoeae via transformation. This creates the rationale for considering the effect of gonococcal therapies on resistance in commensal Neisseria. We illustrate the benefits of this pan-Neisseria strategy by evaluating three contemporary treatment options for N. gonorrhoeae\u2014ceftriaxone plus azithromycin, monotherapy with ceftriaxone and zoliflodacin.<\/jats:p>","DOI":"10.3390\/antibiotics10050515","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Choosing New Therapies for Gonorrhoea: We Need to Consider the Impact on the Pan-Neisseria Genome. A Viewpoint"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-8998","authenticated-orcid":false,"given":"Chris","family":"Kenyon","sequence":"first","affiliation":[{"name":"HIV\/STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium"},{"name":"Division of Infectious Diseases and HIV Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7701, South Africa"},{"name":"STI Reference Center, Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolein","family":"Laumen","sequence":"additional","affiliation":[{"name":"HIV\/STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-5137","authenticated-orcid":false,"given":"Sheeba","family":"Manoharan-Basil","sequence":"additional","affiliation":[{"name":"HIV\/STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1473-3099(18)30225-1","article-title":"Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: A genomic survey","volume":"18","author":"Harris","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kenyon, C., Buyze, J., and Wi, T. (2018). Antimicrobial Consumption and Susceptibility of Neisseria gonorrhoeae: A Global Ecological Analysis. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00329"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lahra, M.M., and Enriquez, R. (2018). Australian Gonococcal Surveillance Programme Annual Report, 2016. Commun. Dis. Intell., 42.","DOI":"10.33321\/cdi.2019.43.13"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yin, Y.-P., Han, Y., Dai, X.-Q., Zheng, H.-P., Chen, S.-C., Zhu, B.-Y., Yong, G., Zhong, N., Hu, L.-H., and Cao, W.-L. (2018). Susceptibility of Neisseria gonorrhoeae to azithromycin and ceftriaxone in China: A retrospective study of national surveillance data from 2013 to 2016. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002499"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wi, T., Lahra, M.M., Ndowa, F., Bala, M., Dillon, J.-A.R., Ramon-Pardo, P., Eremin, S.R., Bolan, G., and Unemo, M. (2017). Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002344"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1177\/0956462420948739","article-title":"Background review for the \u20182020 European guideline for the diagnosis and treatment of gonorrhoea in adults\u2019","volume":"32","author":"Unemo","year":"2021","journal-title":"Int. J. STD AIDS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3181\/00379727-60-15129","article-title":"Adaptability of Gonocoecus to Four Bacteriostatic Agents, Sodium Sulfathiazole, Rivanol Lactate, Promin, and Penicillin","volume":"60","author":"Carpenter","year":"1945","journal-title":"Exp. Biol. Med."},{"key":"ref_8","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":"Barbee","year":"2020","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.3201\/eid2407.172104","article-title":"Effects of Sexual Network Connectivity and Antimicrobial Drug Use on Antimicrobial Resistance inNeisseria gonorrhoeae","volume":"24","author":"Kenyon","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1185449","article-title":"The Population Dynamics and Control of Tuberculosis","volume":"328","author":"Dye","year":"2010","journal-title":"Science"},{"key":"ref_11","first-page":"97","article-title":"Drug resistance in Mycobacterium tuberculosis","volume":"8","author":"Johnson","year":"2006","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tibtech.2012.12.006","article-title":"Combination approaches to combat multidrug-resistant bacteria","volume":"31","author":"Worthington","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3201\/eid0804.010312","article-title":"Antimicrobial Use and Antimicrobial Resistance: A Population Perspective","volume":"8","author":"Lipsitch","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/cid\/ciz365","article-title":"Decreased Cephalosporin Susceptibility of Oropharyngeal Neisseria Species in Antibiotic-using Men Who Have Sex With Men in Hanoi, Vietnam","volume":"70","author":"Dong","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/cid\/ciaa565","article-title":"Markedly Reduced Azithromycin and Ceftriaxone Susceptibility in Commensal Neisseria Species in Clinical Samples From Belgian Men Who Have Sex With Men","volume":"72","author":"Laumen","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, M., Zhang, C., Zhang, X., and Chen, M. (2019). Meningococcal Quinolone Resistance Originated from Several Commensal Neisseria Species. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.01494-19"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1128\/AAC.49.1.137-143.2005","article-title":"Emergence and Spread of Neisseria gonorrhoeae Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan","volume":"49","author":"Ito","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wadsworth, C.B., Arnold, B.J., Sater, M.R.A., and Grad, Y.H. (2018). Azithromycin Resistance through Interspecific Acquisition of an Epistasis-Dependent Efflux Pump Component and Transcriptional Regulator inNeisseria gonorrhoeae. mBio, 9.","DOI":"10.1128\/mBio.01419-18"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Banhart, S., Selb, R., Oehlmann, S., Bender, J., Buder, S., Jansen, K., and Heuer, D. (2021). The mosaic mtr locus as major genetic determinant of azithromycin resistance of Neisseria gonorrhoeae, Germany, 2018. J. Infect. Dis.","DOI":"10.1136\/sextrans-2021-sti.270"},{"key":"ref_20","first-page":"e000205","article-title":"Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages","volume":"4","author":"Yahara","year":"2018","journal-title":"Microb. Genom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/MRM.0000000000000013","article-title":"Antibiotic resistance among commensal Neisseria species","volume":"25","author":"Mechergui","year":"2014","journal-title":"Rev. Med Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s10156-007-0541-8","article-title":"Antimicrobial resistance in clinical isolates of Neisseria subflava from the oral cavities of a Japanese population","volume":"13","author":"Furuya","year":"2007","journal-title":"J. Infect. Chemother."},{"key":"ref_23","first-page":"1","article-title":"Nitrite-producing oral microbiome in adults and children","volume":"10","author":"Washio","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.1128\/JCM.43.11.5721-5732.2005","article-title":"Defining the Normal Bacterial Flora of the Oral Cavity","volume":"43","author":"Aas","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Willis, J.R., and Gabald\u00f3n, T. (2020). The Human Oral Microbiome in Health and Disease: From Sequences to Ecosystems. Microorganisms, 8.","DOI":"10.3390\/microorganisms8020308"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yolken, R., Prandovszky, E., Severance, E.G., Hatfield, G., and Dickerson, F. (2020). The oropharyngeal microbiome is altered in individuals with schizophrenia and mania. Schizophr. Res.","DOI":"10.1016\/j.schres.2020.03.010"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.niox.2020.11.002","article-title":"Association between hypertension, oral microbiome and salivary nitric oxide: A case-control study","volume":"106","author":"Barbadoro","year":"2021","journal-title":"Nitric Oxide"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kraal, L., Abubucker, S., Kota, K., Fischbach, M.A., and Mitreva, M. (2014). The Prevalence of Species and Strains in the Human Microbiome: A Resource for Experimental Efforts. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097279"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"de Block, T., Laumen, J.G.E., Van Dijck, C., Abdellati, S., De Baetselier, I., Manoharan-Basil, S.S., Van den Bossche, D., and Kenyon, C. (2021). Wgs of commensal neisseria reveals acquisition of a new ribosomal protection protein (Msrd) as a possible explanation for high level azithromycin resistance in Belgium. Pathogens, 10.","DOI":"10.3390\/pathogens10030384"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E11988","DOI":"10.1073\/pnas.1810840115","article-title":"Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora","volume":"115","author":"Tedijanto","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Van Dijck, C., Laumen, J.G.E., Manoharan-Basil, S.S., and Kenyon, C. (2020). Commensal Neisseria Are Shared between Sexual Partners: Implications for Gonococcal and Meningococcal Antimicrobial Resistance. Pathogens, 9.","DOI":"10.3390\/pathogens9030228"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/2049-2618-2-41","article-title":"Shaping the oral microbiota through intimate kissing","volume":"2","author":"Kort","year":"2014","journal-title":"Microbiome"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1177\/0956462420957519","article-title":"Screening for STIs in PrEP cohorts results in high levels of antimicrobial consumption","volume":"31","author":"Kenyon","year":"2020","journal-title":"Int. J. STD AIDS"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/QAD.0000000000002020","article-title":"We need to consider collateral damage to resistomes when we decide how frequently to screen for chlamydia\/gonorrhoea in PrEP cohorts","volume":"33","author":"Kenyon","year":"2019","journal-title":"AIDS"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kenyon, C., Manoharan-Basil, S.S., and Van Dijck, C. (2021). Is There a Resistance Threshold for Macrolide Consumption? Positive Evidence from an Ecological Analysis of Resistance Data from Streptococcus pneumoniae, Treponema pallidum, and Mycoplasma genitalium. Microb. Drug Resist.","DOI":"10.1101\/2020.10.13.20212043"},{"key":"ref_36","unstructured":"Abdelatti, S., Gonzales, N., De Block, T., Manoharan-Basil, S., Laumen, J., De Baetselier, I., and Kenyon, C. (2021, January 9\u201312). Intraspecies transformation of msrD gene conferring high-level macrolide resistance in Neisseria subflava. Proceedings of the ECCMID."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0140-6736(07)60235-9","article-title":"Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: A randomised, double-blind, placebo-controlled study","volume":"369","author":"Lammens","year":"2007","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1056\/NEJMoa2002606","article-title":"Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution","volume":"383","author":"Doan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jakobsson, H.E., Jernberg, C., Andersson, A.F., Sj\u00f6lund-Karlsson, M., Jansson, J.K., and Engstrand, L. (2010). Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009836"},{"key":"ref_40","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":"ref_41","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1177\/0956462415618837","article-title":"2015 European guideline on the management of Chlamydia trachomatis infections","volume":"27","author":"Lanjouw","year":"2015","journal-title":"Int. J. STD AIDS"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"183S","DOI":"10.1378\/chest.113.3_Supplement.183S","article-title":"Community-acquired pneumonia guidelines\u2014An international comparison: A view from Europe","volume":"113","author":"Woodhead","year":"1998","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1111\/jdv.13849","article-title":"2016 European guideline on Mycoplasma genitalium infections","volume":"30","author":"Jensen","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1038\/s41467-018-07235-5","article-title":"Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection","volume":"9","author":"Pandey","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1093\/molbev\/msaa282","article-title":"Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage","volume":"38","author":"Osnes","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jgar.2020.10.022","article-title":"Gonorrhoea treatment combined with population-level general cephalosporin and quinolone consumption may select for Neisseria gonorrhoeae antimicrobial resistance at the levels of NG-MAST genogroup: An ecological study in Europe","volume":"23","author":"Kenyon","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1093\/jac\/dkab024","article-title":"High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018","volume":"76","author":"Unemo","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_48","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":"ref_49","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3389\/fmicb.2015.01377","article-title":"Genetic Resistance Determinants, In Vitro Time-Kill Curve Analysis and Pharmacodynamic Functions for the Novel Topoisomerase II Inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae","volume":"6","author":"Foerster","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1128\/AAC.04456-14","article-title":"Characterization of the Novel DNA Gyrase Inhibitor AZD0914: Low Resistance Potential and Lack of Cross-Resistance in Neisseria gonorrhoeae","volume":"59","author":"Alm","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"iv47","DOI":"10.1136\/sextrans-2013-051020","article-title":"The role of core groups in the emergence and dissemination of antimicrobial-resistantN gonorrhoeae","volume":"89","author":"Lewis","year":"2013","journal-title":"Sex. Transm. Infect."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S1473-3099(02)00393-6","article-title":"Allodemics","volume":"2","author":"Baquero","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13756-020-00764-z","article-title":"Gonococcal resistance can be viewed productively as part of a syndemic of antimicrobial resistance: An ecological analysis of 30 European countries","volume":"9","author":"Kenyon","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/0277-9536(94)90202-X","article-title":"Epidemiology and the web of causation: Has anyone seen the spider?","volume":"39","author":"Krieger","year":"1994","journal-title":"Soc. Sci. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"674","DOI":"10.2105\/AJPH.86.5.674","article-title":"Choosing a future for epidemiology: II. From black box to Chinese boxes and eco-epidemiology","volume":"86","author":"Susser","year":"1996","journal-title":"Am. J. Public Health"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/5\/515\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:56:31Z","timestamp":1760162191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/5\/515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["antibiotics10050515"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10050515","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,1]]}}}