{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:34:05Z","timestamp":1791221645088,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Program on Emerging and Reemerging Infectious Diseases of the Japan Agency for Medical Research and Development, AMED","award":["JP25fk0108697"],"award-info":[{"award-number":["JP25fk0108697"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The DNA synthesis inhibitor zoliflodacin (ZFD) is expected to be effective against strains resistant to therapeutic agents for Neisseria gonorrhoeae infection. In addition to ZFD, we investigated the susceptibility of N. gonorrhoeae strains to ceftriaxone (CTRX), ciprofloxacin (CPFX), garenoxacin (GRNX), and sitafloxacin (STFX). Minimum inhibitory concentration values for ZFD and four other drugs were determined for 147 strains of N. gonorrhoeae isolated at medical institutions in Hyogo Prefecture, Japan, from 2015 to 2022. Amino acid alterations in gyrA, gyrB, parC, and parE were examined by polymerase chain reaction and sequencing analysis. Sequence type (ST) was determined for epidemiological analysis, and N. gonorrhoeae strains were classified. The non-susceptibility rate was not observed in CTRX. The lowest non-susceptibility rate was observed in ZFD (39.5%) compared to CPFX (80.3%), GRNX (83.7%), and STFX (65.3%) (all p &lt; 0.0001). The most common amino acid alterations in gyrA and parC had non-susceptibility rates exceeding 80% to quinolones except ZFD, suggesting that these alterations may have influenced the resistance trend. STs were different between isolates in 2015 and those in 2020 and later. ZFD showed potent antimicrobial activity against N. gonorrhoeae strains that are highly resistant to quinolones. It may become a new option in the treatment of gonococcal infections.<\/jats:p>","DOI":"10.3390\/pathogens14080831","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Susceptibility of Neisseria gonorrhoeae to Zoliflodacin and Quinolones in Hyogo Prefecture, Japan"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-361X","authenticated-orcid":false,"given":"Takashi","family":"Yurube","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Shigemura","sequence":"additional","affiliation":[{"name":"Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo 173-8605, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurino","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taishi","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nami","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotoko","family":"Kotani","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Horii","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Hyogo Clinical Laboratory Corporation, 5-6-2, Aoyamanishi, Himeji 671-2224, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4787-4333","authenticated-orcid":false,"given":"Kayo","family":"Osawa","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University, 2-6-2 Otani-cho, Nagata-ku, Kobe 653-0838, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","unstructured":"(2024, December 04). Gonorrhoa (Neisseria gonorrhoeae). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/gonorrhoea-(neisseria-gonorrhoeae-infection)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10096-024-04968-8","article-title":"Eur Management and prevention of Neisseria meningitidis and Neisseria gonorrhoeae infections in the context of evolving antimicrobial resistance trends","volume":"44","author":"Marshall","year":"2025","journal-title":"J. Clin. Microbiol. Infect. Dis."},{"key":"ref_3","first-page":"213","article-title":"Antimicrobial resistance expressed by Neisseria gonorrhoeae: A major global public health problem in the 21st Century","volume":"10","author":"Unemo","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_4","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_5","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":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1128\/AAC.40.10.2437","article-title":"Uncommon occurrence of alterations in the gyrB gene associated with quinolone resistance in clinical isolates of Neisseria gonorrhoeae","volume":"40","author":"Deguchi","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1034\/j.1600-0463.2002.1100909.x","article-title":"Mutations in gyrA, gyrB, parC, and parE in quinolone-resistant strains of Neisseria gonorrhoeae","volume":"110","author":"Rahman","year":"2002","journal-title":"APMIS"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1097\/00007435-200212000-00008","article-title":"Characterization of ciprofloxacin resistance in Neisseria gonorrhoeae isolates in Canada","volume":"29","author":"Ng","year":"2002","journal-title":"Sex. Transm. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1093\/jac\/dkp098","article-title":"Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes","volume":"63","author":"Unemo","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","unstructured":"(2024, December 04). PubMLST. Available online: https:\/\/pubmlst.org\/organisms\/neisseria-spp."},{"key":"ref_11","unstructured":"(2024, December 04). CLSI. Available online: https:\/\/clsi.org\/ast-2024."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00863-20","DOI":"10.1128\/AAC.00863-20","article-title":"Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China. 2014 to 2018","volume":"65","author":"Le","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_14","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":"Antimicrob. Chemother."},{"key":"ref_15","first-page":"mgen001006","article-title":"Antimicrobial-Resistant Working Group. Genomic analysis of 1710 surveillance-based Neisseria gonorrhoeae isolates from the USA in 2019 identifies predominant strain types and chromosomal antimicrobial-resistance determinants","volume":"9","author":"Reimche","year":"2023","journal-title":"Microb. Genom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1093\/jac\/dkae075","article-title":"Recent dynamics in Neisseria gonorrhoeae genomic epidemiology in Brazil: Antimicrobial resistance and genomic lineages in 2017\u20132020 compared to 2015\u20132016","volume":"79","author":"Golparian","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","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."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3201\/eid2507.190172","article-title":"Identification of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, China","volume":"25","author":"Chen","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/S1473-3099(22)00520-5","article-title":"The need for a commercial test using the penA60 allele to identify ceftriaxone-resistant Neisseria gonorrhoeae","volume":"22","author":"Tickner","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_20","unstructured":"GARDP (2024, December 04). Positive Results in Largest Pivotal Phase 3 Trial of a Novel Antibiotic to Treat Gonorrhoea. Available online: https:\/\/gardp.org\/positive-results-announced-in-largest-pivotal-phase-3-trial-of-a-first-in-class-oral-antibiotic-to-treat-uncomplicated-gonorrhoea\/."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., and Marusza, W. (2022). Molecular mechanisms of drug resistance and epidemiology of multidrug-resistant variants of Neisseria gonorrhoeae. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810499"},{"key":"ref_22","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":"ref_23","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1128\/AAC.04320-14","article-title":"Azithromycin resistance and its mechanism in Neisseria gonorrhoeae strains in Hyogo, Japan","volume":"59","author":"Shigemura","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"001533","DOI":"10.1099\/jmm.0.001533","article-title":"Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015\u20132019","volume":"71","author":"Miura","year":"2022","journal-title":"J. Med. Microbiol."},{"key":"ref_25","unstructured":"WHO (2024, December 04). Updated Recommendations for the Treatment of Neisseria gonorrhoeae, Chlamydia trachomatis and Treponema pallidum (Syphilis), and New Recommendations on Syphilis Testing and Partner Service. Available online: https:\/\/iris.who.int\/bitstream\/handle\/10665\/378228\/B09099-eng.pdf."},{"key":"ref_26","unstructured":"CDC (2024, December 04). Clinical Treatment of Gonorrhoea, Available online: https:\/\/www.cdc.gov\/gonorrhea\/hcp\/clinical-care\/index.html."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1093\/clinids\/20.Supplement_1.S47","article-title":"Drugs of choice for the treatment of uncomplicated gonococcal infections","volume":"20","author":"Moran","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"dlae040","DOI":"10.1093\/jacamr\/dlae040","article-title":"Molecular epidemiological and antimicrobial-resistant mechanisms analysis of prolonged Neisseria gonorrhoeae collection between 1971 and 2005 in Japan","volume":"6","author":"Kagawa","year":"2024","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jacobsson, S., Cole, M.J., Spiteri, G., Day, M., Unemo, M., and Euro-GASP Network (2021). Associations between antimicrobial susceptibility\/resistance of Neisseria gonorrhoeae isolates in the European Union\/European Economic Area and patients\u2019 gender, sexual orientation and anatomical site of infection, 2009\u20132016. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-05931-0"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"255","DOI":"10.15585\/mmwr.mm7312a2","article-title":"Ceftriaxone-Resistant Gonorrhea\u2013China, 2022","volume":"73","author":"Zhu","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Al-Maslamani, M., Elmagboul, E.B.I., Puthiyottil, A., Chemaitelly, H., Varghese, M.K., Al Romaihi, H.E., Al-Thani, M.H., Al Khal, A., Unemo, M., and Abu-Raddad, L.J. (2022). First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017\u20132020. PLoS ONE., 17.","DOI":"10.1371\/journal.pone.0264737"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhong, J., Le, W., Li, X., and Su, X. (2024). Evaluating the efficacy of different antibiotics against Neisseria gonorrhoeae: A pharmacokinetic\/pharmacodynamic analysis. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-023-08938-x"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1021\/acsinfecdis.4c00438","article-title":"Interactions between Zoliflodacin and Neisseria gonorrhoeae gyrase and topoisomerase IV: Enzymological basis for cellular targeting. enzymological basis for cellular targeting","volume":"10","author":"Collins","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gaspari, V., Djusse, M.E., Morselli, S., Rapparini, L., Foschi, C., Ambretti, S., Lazzarotto, T., Piraccini, B.M., and Marangoni, A. (2023). Non-pathogenic Neisseria species of the oropharynx as a reservoir of antimicrobial resistance: A cross-sectional study. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1308550"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/8\/831\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:32:49Z","timestamp":1760034769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/8\/831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["pathogens14080831"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14080831","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]}}}