{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:09:07Z","timestamp":1793419747172,"version":"4.5.0"},"reference-count":164,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T00:00:00Z","timestamp":1462492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2016,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Neisseria gonorrhoeae<\/jats:italic>is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.<\/jats:p>","DOI":"10.1128\/microbiolspec.ei10-0009-2015","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T16:08:56Z","timestamp":1465920536000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":207,"title":["Antimicrobial Resistance Expressed by<i>Neisseria gonorrhoeae<\/i>: A Major Global Public Health Problem in the 21st Century"],"prefix":"10.1128","volume":"4","author":[{"given":"Magnus","family":"Unemo","sequence":"first","affiliation":[{"name":"WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, \u00d6rebro University Hospital, SE-701 85 \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"del Rio","sequence":"additional","affiliation":[{"name":"Hubert Department of Global Health, Rollins School of Public Health of Emory University and Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"},{"name":"Veterans Affairs Medical Center (Atlanta), Decatur, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"World Health Organization Department of Reproductive Health and Research. 2012. Global Action Plan To Control the Spread and Impact of Antimicrobial Resistance in Neisseria gonorrhoeae . World Health Organization Geneva Switzerland."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Bignell C Unemo M. 2013. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS 24: 85\u201392. [PubMed][CrossRef]","DOI":"10.1177\/0956462412472837"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","unstructured":"Cohen MS Hoffman IF Royce RA Kazembe P Dyer JR Daly CC Zimba D Vernazza PL Maida M Fiscus SA Eron JJ Jr. 1997. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 349: 1868\u20131873. [CrossRef] [PubMed][CrossRef]","DOI":"10.1016\/S0140-6736(97)02190-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Tapsall JW Ndowa F Lewis DA Unemo M. 2009. Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae . Expert Rev Anti Infect Ther 7: 821\u2013834.","DOI":"10.1586\/eri.09.63"},{"key":"e_1_3_2_6_2","unstructured":"Unemo M Ison C. 2013. Gonorrhoea. p 21. In Unemo M Ballard R Ison C Lewis D Ndowa F Peeling R (ed) Laboratory Diagnosis of Sexually Transmitted Infections Including Human Immunodeficiency Virus . World Health Organization Geneva Switzerland."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","unstructured":"Del Rio C Stephens DS Knapp JS Rice RJ Schalla WO. 1989. Comparison of isolates of Neisseria gonorrhoeae causing meningitis and report of gonococcal meningitis in a patient with C8 deficiency. J Clin Microbiol 27:1045\u20131049. [PubMed]","DOI":"10.1128\/jcm.27.5.1045-1049.1989"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","unstructured":"Newman LM Rowley J Vander Hoorn S Wijesooriya NS Unemo M Low N Stevens G Kiarie J Temmerman M. 2015. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS Med 10 (12) : e0143304. [PubMed][CrossRef]","DOI":"10.1371\/journal.pone.0143304"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","unstructured":"C\u00e1mara J Serra J Ayats J Bastida T Carnicer-Pont D Andreu A Ardanuy C. 2012. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia Spain. J Antimicrob Chemother 67: 1858\u20131860. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dks162"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"Ohnishi M Golparian D Shimuta K Saika T Hoshina S Iwasaku K Nakayama S Kitawaki J Unemo M. 2011. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea? Detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 55: 3538\u20133545. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00325-11"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","unstructured":"Unemo M Golparian D Nicholas R Ohnishi M Gallay A Sednaoui P. 2012. High-level cefixime- and ceftriaxone-resistant N. gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 56: 1273\u20131280. [PubMed][CrossRef]","DOI":"10.1128\/AAC.05760-11"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","unstructured":"Unemo M Nicholas RA. 2012. Emergence of multidrug-resistant extensively drug-resistant and untreatable gonorrhea. Future Microbiol 7: 1401\u20131422. [PubMed][CrossRef]","DOI":"10.2217\/fmb.12.117"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","unstructured":"Unemo M Shafer WM. 2014. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st Century: past evolution and future. Clin Microbiol Rev 27: 587\u2013613. [PubMed][CrossRef]","DOI":"10.1128\/CMR.00010-14"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","unstructured":"Bolan GA Sparling PF Wasserheit JN. 2012. The emerging threat of untreatable gonococcal infection. N Engl J Med 366: 485\u2013487. [PubMed][CrossRef]","DOI":"10.1056\/NEJMp1112456"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","unstructured":"Ison CA. 2012. Antimicrobial resistance in sexually transmitted infections in the developed world: implications for rational treatment. Curr Opin Infect Dis 25: 73\u201378. [PubMed][CrossRef]","DOI":"10.1097\/QCO.0b013e32834e9a6a"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"Unemo M Shafer WM. 2011. Antibiotic resistance in Neisseria gonorrhoeae : origin evolution and lessons learned for the future. Ann N Y Acad Sci 1230: E19\u2013E28. [PubMed][CrossRef]","DOI":"10.1111\/j.1749-6632.2011.06215.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","unstructured":"Whiley DM Goire N Lahra MM Donovan B Limnios AE Nissen MD Sloots TP. 2012. The ticking time bomb: escalating antibiotic resistance in Neisseria gonorrhoeae is a public health disaster in waiting. J Antimicrob Chemother 67: 2059\u20132061. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dks188"},{"key":"e_1_3_2_18_2","unstructured":"Groopman J. 1 October 2012. Sex and the superbug\u2014the rise of drug-resistant gonorrhea. The New Yorker New York NY."},{"key":"e_1_3_2_19_2","unstructured":"Centers for Disease Control and Prevention. 2012. Cephalosporin-Resistant Neisseria gonorrhoeae Public Health Response Plan . Centers for Disease Control and Prevention Atlanta GA."},{"key":"e_1_3_2_20_2","unstructured":"European Centre for Disease Prevention and Control. 2012. Response Plan To Control and Manage the Threat of Multidrug-Resistant Gonorrhoea in Europe . European Centre for Disease Prevention and Control Stockholm Sweden."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","unstructured":"Ndowa F Lusti-Narasimhan M Unemo M. 2012. The serious threat of multidrug-resistant and untreatable gonorrhoea: the pressing need for global action to control the spread of antimicrobial resistance and mitigate the impact on sexual and reproductive health. Sex Transm Infect 88: 317\u2013318. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2012-050674"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","unstructured":"Unemo M. 2015. Current and future antimicrobial treatment of gonorrhoea\u2014the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infect Dis 15: 364. [PubMed][CrossRef]","DOI":"10.1186\/s12879-015-1029-2"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","unstructured":"Ashford WA Golash RG Henning VG. 1976. Penicillinase producing Neisseria gonorrhoeae . Lancet ii: 657\u2013658. [CrossRef]","DOI":"10.1016\/S0140-6736(76)92467-3"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","unstructured":"Phillips I. 1976. Beta-lactamase producing penicillin-resistant gonococcus. Lancet ii: 656\u2013657. [CrossRef]","DOI":"10.1016\/S0140-6736(76)92466-1"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","unstructured":"Morse SA Johnson SR Biddle JW Roberts MC. 1986. High-level tetracycline resistance in Neisseria gonorrhoeae is result of acquisition of streptococcal tetM determinant. Antimicrob Agents Chemother 30: 664\u2013670. [PubMed][CrossRef]","DOI":"10.1128\/AAC.30.5.664"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","unstructured":"Nagaev I Bj\u00f6rkman J Andersson DI Hughes D. 2001. Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus . Mol Microbiol 40: 433\u2013439. [PubMed][CrossRef]","DOI":"10.1046\/j.1365-2958.2001.02389.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","unstructured":"Rozen DE McGee L Levin BR Klugman KP. 2007. Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae . Antimicrob Agents Chemother 51: 412\u2013416. [PubMed][CrossRef]","DOI":"10.1128\/AAC.01161-06"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","unstructured":"Trzcinski K Thompson CM Gilbey AM Dowson CG Lipsitch M. 2006. Incremental increase in fitness cost with increased beta-lactam resistance in pneumococci evaluated by competition in an infant rat nasal colonization model. J Infect Dis 193: 1296\u20131303. [PubMed][CrossRef]","DOI":"10.1086\/501367"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","unstructured":"Kunz AN Begum AA Wu H D\u2019Ambrozio JA Robinson JM Shafer WM Bash MC Jerse AE. 2012. Impact of fluoroquinolone resistance mutations on gonococcal fitness and in vivo selection for compensatory mutations. J Infect Dis 205: 1821\u20131829. [PubMed][CrossRef]","DOI":"10.1093\/infdis\/jis277"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","unstructured":"Warner DM Shafer WM Jerse AE. 2008. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE Efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol Microbiol 70: 462\u2013478. [PubMed][CrossRef]","DOI":"10.1111\/j.1365-2958.2008.06424.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","unstructured":"Kampmeier RH. 1983. Introduction of sulfonamide therapy for gonorrhea. Sex Transm Dis 10: 81\u201384. [PubMed][CrossRef]","DOI":"10.1097\/00007435-198304000-00007"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","unstructured":"Dunlop EMC. 1949. Gonorrhoea and the sulphonamides. Br J Vener Dis 25: 81\u201383. [PubMed]","DOI":"10.1136\/sti.25.2.81"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","unstructured":"Fermer C Kristiansen BE Sk\u00f6ld O Swedberg G. 1995. Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species. J Bacteriol 177: 4669\u20134675. [PubMed]","DOI":"10.1128\/jb.177.16.4669-4675.1995"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","unstructured":"Johnson SR Morse SA. 1988. Antibiotic resistance in Neisseria gonorrhoeae : genetics and mechanisms of resistance. Sex Transm Dis 15: 217\u2013224. [CrossRef]","DOI":"10.1097\/00007435-198810000-00008"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","unstructured":"Swedberg G Ferm\u00e9r C Sk\u00f6ld O. 1993. Point mutations in the dihydropteroate synthase gene causing sulfonamide resistance. Adv Exp Med Biol 338: 555\u2013558. [PubMed][CrossRef]","DOI":"10.1007\/978-1-4615-2960-6_113"},{"key":"e_1_3_2_36_2","unstructured":"Mahoney JF Ferguson C Buchholtz M van Slyke CJ. 1943. The use of penicillin sodium in the treatment of sulfonamide-resistant gonorrhea in men. A preliminary report. Am J Gonorr Vener Dis 27: 525\u2013528."},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","unstructured":"Van Slyke CJ Arnold RC Buchholtz M. 1943. Penicillin therapy in sulfonamide-resistant gonorrhea in men. Am J Public Health Nations Health 33: 1392\u20131394. [PubMed][CrossRef]","DOI":"10.2105\/AJPH.33.12.1392"},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","unstructured":"Lewis DA. 2010. The gonococcus fights back: is this time a knock out? Sex Transm Infect 86: 415\u2013421. [PubMed][CrossRef]","DOI":"10.1136\/sti.2010.042648"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","unstructured":"Jaffe HW Biddle JW Thornsberry C Johnson RE Kaufman RE Reynolds GH Wiesner PJ. 1976. National gonorrhea therapy monitoring study: in vitro antibiotic susceptibility and its correlation with treatment results. N Engl J Med 294: 5\u20139. [PubMed][CrossRef]","DOI":"10.1056\/NEJM197601012940102"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"Martin JE Jr Lester A Price EV Schmale JD. 1970. Comparative study of gonococcal susceptibility to penicillin in the United States 1955\u20131969. J Infect Dis 122: 459\u2013461. [PubMed][CrossRef]","DOI":"10.1093\/infdis\/122.5.459"},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","unstructured":"Reyn A Korner B Bentzon MW. 1958. Effects of penicillin streptomycin and tetracycline on N. gonorrhoeae isolated in 1944 and in 1957. Br J Vener Dis 34: 227\u2013239. [CrossRef]","DOI":"10.1136\/sti.34.4.227"},{"key":"e_1_3_2_42_2","unstructured":"Unemo M Nicholas RA Davies C Jerse A Shafer WM. 2013. Molecular mechanisms of antibiotic resistance expressed by the pathogenic Neisseria p 245\u2013268. In Genco C Wetzler L (ed) Neisseria\u2014Molecular Mechanisms of Pathogenic Neisseria . Caister Academic Press London United Kingdom."},{"key":"e_1_3_2_43_2","unstructured":"Amies CR. 1967. Development of resistance of gonococci to penicillin. An eight-year study. Can Med Ass J 96: 33\u201335. [PubMed]"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","unstructured":"Franks AG. 1946. Successful combined treatment of penicillin-resistant gonorrhea. Am J Med Sci 211: 553\u2013555. [PubMed][CrossRef]","DOI":"10.1097\/00000441-194605000-00005"},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","unstructured":"Faruki H Kohmescher RN McKinney WP Sparling PF. 1985. A community-based outbreak of infection with penicillin-resistant Neisseria gonorrhoeae not producing penicillinase (chromosomally mediated resistance). N Engl J Med 313: 607\u2013611. [PubMed][CrossRef]","DOI":"10.1056\/NEJM198509053131004"},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","unstructured":"Faruki H Sparling PF. 1986. Genetics of resistance in a non-beta-lactamase-producing gonococcus with relatively high-level penicillin resistance. Antimicrob Agents Chemother 30: 856\u2013860. [PubMed][CrossRef]","DOI":"10.1128\/AAC.30.6.856"},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","unstructured":"Bala M Kakran M Singh V Sood S Ramesh V Members of WHO GASP SEAR Network. 2013. Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012: a retrospective analysis. Sex Transm Infect 89 (Suppl 4) : iv28\u2013iv35. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2012-050904"},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","unstructured":"Dillon JA Trecker MA Thakur SD Gonococcal Antimicrobial Surveillance Program Network in Latin America and the Caribbean 1990\u20132011. 2013. Two decades of the gonococcal antimicrobial surveillance program in South America and the Caribbean: challenges and opportunities. Sex Transm Infect 89 (Suppl 4) : iv36\u2013iv41. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2012-050905"},{"key":"e_1_3_2_49_2","doi-asserted-by":"crossref","unstructured":"Kirkcaldy RD Kidd S Weinstock HS Papp JR Bolan GA. 2013. Trends in antimicrobial resistance in Neisseria gonorrhoeae in the USA: the Gonococcal Isolate Surveillance Project (GISP) January 2006\u2013June 2012. Sex Transm Infect 89 (Suppl 4) : iv5\u2013iv10. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2013-051162"},{"key":"e_1_3_2_50_2","doi-asserted-by":"crossref","unstructured":"Kubanova A Frigo N Kubanov A Sidorenko S Priputnevich T Vachnina T Al-Khafaji N Polevshikova S Solomka V Domeika M Unemo M. 2008. National surveillance of antimicrobial susceptibility in Neisseria gonorrhoeae in 2005-2006 and recommendations of first-line antimicrobial drugs for gonorrhoea treatment in Russia. Sex Transm Infect 84: 285\u2013289. [PubMed][CrossRef]","DOI":"10.1136\/sti.2007.029033"},{"key":"e_1_3_2_51_2","doi-asserted-by":"crossref","unstructured":"Lahra MM Lo YR Whiley DM. 2013. Gonococcal antimicrobial resistance in the Western Pacific region. Sex Transm Infect 89 (Suppl 4) : iv19\u2013iv23. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2012-050906"},{"key":"e_1_3_2_52_2","doi-asserted-by":"crossref","unstructured":"Martin IM Hoffmann S Ison CA ESSTI Network. 2006. European Surveillance of Sexually Transmitted Infections (ESSTI): the first combined antimicrobial susceptibility data for Neisseria gonorrhoeae in Western Europe. J Antimicrob Chemother 58: 587\u2013593. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkl265"},{"key":"e_1_3_2_53_2","doi-asserted-by":"crossref","unstructured":"Ndowa FJ Francis JM Machiha A Faye-Kette H Fonkoua MC. 2013. Gonococcal antimicrobial resistance: perspectives from the African region. Sex Transm Infect 89 (Suppl 4) : iv11\u2013iv15. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2012-050907"},{"key":"e_1_3_2_54_2","doi-asserted-by":"crossref","unstructured":"Spiteri G Cole M Unemo M Hoffmann S Ison C van de Laar M. 2013. The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP)\u2014a sentinel approach in the European Union (EU)\/European Economic Area (EEA). Sex Transm Infect 89 (Suppl 4) : iv16\u2013iv18. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2013-051117"},{"key":"e_1_3_2_55_2","doi-asserted-by":"crossref","unstructured":"Unemo M Ison CA Cole M Spiteri G van de Laar M Khotenashvili L. 2013. Gonorrhoea and gonococcal antimicrobial resistance surveillance networks in the WHO European region including the independent countries of the former Soviet Union. Sex Transm Infect 89 (Suppl 4) : iv42\u2013iv46. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2012-050909"},{"key":"e_1_3_2_56_2","doi-asserted-by":"crossref","unstructured":"Helm RA Barnhart MM Seifert HS. 2007. pilQ missense mutations have diverse effects on PilQ multimer formation piliation and pilus function in Neisseria gonorrhoeae . J Bacteriol 189: 3198\u20133207. [PubMed][CrossRef]","DOI":"10.1128\/JB.01833-06"},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","unstructured":"Easmon CS Forster GE Walker GD Ison CA Harris JR Munday PE. 1984. Spectinomycin as initial treatment for gonorrhoea. Br Med J 289: 1032\u20131034. [CrossRef]","DOI":"10.1136\/bmj.289.6451.1032"},{"key":"e_1_3_2_58_2","doi-asserted-by":"crossref","unstructured":"Judson FN Ehret JM Handsfield HH. 1985. Comparative study of ceftriaxone and spectinomycin for treatment of pharyngeal and anorectal gonorrhea. JAMA 253: 1417\u20131419. [PubMed][CrossRef]","DOI":"10.1001\/jama.253.10.1417"},{"key":"e_1_3_2_59_2","doi-asserted-by":"crossref","unstructured":"Stolz E Zwart HG Michel MF. 1975. Activity of eight antimicrobial agents in vitro against N. gonorrhoeae . Br J Vener Dis 51: 257\u2013264. [CrossRef]","DOI":"10.1136\/sti.51.4.257"},{"key":"e_1_3_2_60_2","doi-asserted-by":"crossref","unstructured":"Boslego JW Tramont EC Takafuji ET Diniega BM Mitchell BS Small JW Khan WN Stein DC. 1987. Effect of spectinomycin use on the prevalence of spectinomycin-resistant and penicillinase-producing Neisseria gonorrhoeae . N Engl J Med 317: 272\u2013278. [PubMed][CrossRef]","DOI":"10.1056\/NEJM198707303170504"},{"key":"e_1_3_2_61_2","doi-asserted-by":"crossref","unstructured":"Lee H Unemo M Kim HJ Seo Y Lee K Chong Y. 2015. Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea. J Antimicrob Chemother 70: 2536\u20132542. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkv146"},{"key":"e_1_3_2_62_2","doi-asserted-by":"crossref","unstructured":"Lindberg M Ringertz O Sandstr\u00f6m E. 1982. Treatment of pharyngeal gonorrhoea due to \u03b2-lactamase-producing gonococci. Br J Vener Dis 58: 101\u2013104. [PubMed]","DOI":"10.1136\/sti.58.2.101"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","unstructured":"Moran JS. 1995. Treating uncomplicated Neisseria gonorrhoeae infections: is the anatomic site of infection important? Sex Transm Dis 22: 39\u201347. [PubMed][CrossRef]","DOI":"10.1097\/00007435-199501000-00007"},{"key":"e_1_3_2_64_2","doi-asserted-by":"crossref","unstructured":"Moran JS Levine WC. 1995. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis 20 (Suppl 1) : S47\u2013S65. [PubMed][CrossRef]","DOI":"10.1093\/clinids\/20.Supplement_1.S47"},{"key":"e_1_3_2_65_2","doi-asserted-by":"crossref","unstructured":"Galimand M Gerbaud G Courvalin P. 2000. Spectinomycin resistance in Neisseria spp. due to mutations in 16S rRNA. Antimicrob Agents Chemother 44: 1365\u20131366. [PubMed][CrossRef]","DOI":"10.1128\/AAC.44.5.1365-1366.2000"},{"key":"e_1_3_2_66_2","doi-asserted-by":"crossref","unstructured":"Unemo M Fasth O Fredlund H Limnios A Tapsall JW. 2009. Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes. J Antimicrob Chemother 63: 1142\u20131151. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkp098"},{"key":"e_1_3_2_67_2","doi-asserted-by":"crossref","unstructured":"Unemo M Golparian D Skogen V Olsen AO Moi H Syversen G Hjelmevoll SO. 2013. Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism (mutated ribosomal protein S5) verified in Norway. Antimicrob Agents Chemother 57: 1057\u20131061. [PubMed][CrossRef]","DOI":"10.1128\/AAC.01775-12"},{"key":"e_1_3_2_68_2","doi-asserted-by":"crossref","unstructured":"Ilina EN Malakhova MV Bodoev IN Oparina NY Filimonova AV Govorun VM. 2013. Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae . Front Microbiol 4: 186. [PubMed][CrossRef]","DOI":"10.3389\/fmicb.2013.00186"},{"key":"e_1_3_2_69_2","doi-asserted-by":"crossref","unstructured":"Tanaka M Nakayama H Haraoka M Saika T. 2000. Antimicrobial resistance of Neisseria gonorrhoeae and high prevalence of ciprofloxacin-resistant isolates in Japan 1993 to 1998. J Clin Microbiol 38: 521\u2013525. [PubMed]","DOI":"10.1128\/JCM.38.2.521-525.2000"},{"key":"e_1_3_2_70_2","doi-asserted-by":"crossref","unstructured":"Tanaka M Kumazawa J Matsumoto T Kobayashi I. 1994. High prevalence of Neisseria gonorrhoeae strains with reduced susceptibility to fluoroquinolones in Japan. Genitourin Med 70: 90\u201393. [CrossRef]","DOI":"10.1136\/sti.70.2.90"},{"key":"e_1_3_2_71_2","doi-asserted-by":"crossref","unstructured":"Berglund T Unemo M Olc\u00e9n P Giesecke J Fredlund H. 2002. One year of Neisseria gonorrhoeae isolates in Sweden: the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure. Int J STD AIDS 13: 109\u2013114. [PubMed][CrossRef]","DOI":"10.1258\/0956462021924730"},{"key":"e_1_3_2_72_2","unstructured":"Patrick D Shaw C Rekart ML. 1995. Neisseria gonorrhoeae with decreased susceptibility to ciprofloxacin in British Columbia: an imported phenomenon. Can Common Dis Rep 21: 137\u2013139. [PubMed]"},{"key":"e_1_3_2_73_2","doi-asserted-by":"crossref","unstructured":"Su X Lind I. 2001. Molecular basis of high-level ciprofloxacin resistance in Neisseria gonorrhoeae strains isolated from Denmark from 1995\u20131998. Antimicrob Agents Chemother 45: 117\u2013123. [PubMed][CrossRef]","DOI":"10.1128\/AAC.45.1.117-123.2001"},{"key":"e_1_3_2_74_2","doi-asserted-by":"crossref","unstructured":"Iverson CJ Wang SA Lee MV Ohye RG Trees DL Knapp JS Effler PV O\u2019Connor NP Levine WC. 2004. Fluoroquinolone-resistance among Neisseria gonorrhoeae isolates in Hawaii 1990\u20132000: role of foreign importation and endemic spread. Sex Transm Dis 31: 702\u2013708. [PubMed][CrossRef]","DOI":"10.1097\/01.olq.0000145846.45781.a4"},{"key":"e_1_3_2_75_2","unstructured":"Centers for Disease Control and Prevention. 2004. Increases in fluoroquinolone-resistant Neisseria gonorrhoeae among men who have sex with men\u2014United States 2003 and revised recommendations for gonorrhea treatment 2004. MMWR Morb Mortal Wkly Rep 53: 335\u2013338. [PubMed]"},{"key":"e_1_3_2_76_2","unstructured":"Centers for Disease Control and Preventio. 2007. Update to CDC\u2019s Sexually Transmitted Diseases Treatment Guidelines 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 56: 332\u2013336. [PubMed]"},{"key":"e_1_3_2_77_2","doi-asserted-by":"crossref","unstructured":"Douthwaite S Champney WS. 2001. Structures of ketolides and macrolides determine their mode of interaction with the ribosomal target site. J Antimicrob Chemother 48 (Suppl T1) : 1\u20138.","DOI":"10.1093\/jac\/48.suppl_2.1"},{"key":"e_1_3_2_78_2","doi-asserted-by":"crossref","unstructured":"Dillon JA Ruben M Li H Borthagaray G M\u00e1rquez C Fiorito S Galarza P Portilla JL Le\u00f3n L Agudelo CI Sanabria OM Maldonado A Prabhakar P. 2006. Challenges in the control of gonorrhea in South America and the Caribbean: monitoring the development of resistance to antibiotics. Sex Transm Dis 33: 87\u201395. [PubMed][CrossRef]","DOI":"10.1097\/01.olq.0000187231.28812.29"},{"key":"e_1_3_2_79_2","doi-asserted-by":"crossref","unstructured":"Starnino S GASP-LAC Working Group Galarza P Carvallo ME Benzaken AS Ballesteros AM Cruz OM Hernandez AL Carbajal JL Borthagaray G Payares D Dillon JA. 2012. Retrospective analysis of antimicrobial susceptibility trends (2000-2009) in Neisseria gonorrhoeae isolates from countries in Latin America and the Caribbean show evolving resistance to ciprofloxacin azithromycin and decreased susceptibility to ceftrixone. Sex Transm Dis 39: 813\u2013821. [PubMed][CrossRef]","DOI":"10.1097\/OLQ.0b013e3182631c9f"},{"key":"e_1_3_2_80_2","doi-asserted-by":"crossref","unstructured":"Kubanova A Frigo N Kubanov A Sidorenko S Lesnaya I Polevshikova S Solomka V Bukanov N Domeika M Unemo M. 2010. The Russian gonococcal antimicrobial susceptibility programme (RU-GASP)\u2014national resistance prevalence in 2007 and 2008 and trends during 2005\u20132008. Euro Surveill 15 (14) : 19533. [PubMed]","DOI":"10.2807\/ese.15.14.19533-en"},{"key":"e_1_3_2_81_2","doi-asserted-by":"crossref","unstructured":"Chisholm SA Dave J Ison CA. 2010. High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes. Antimicrob Agents Chemother 54: 3812\u20133816. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00309-10"},{"key":"e_1_3_2_82_2","doi-asserted-by":"crossref","unstructured":"Lynagh Y Mac Aog\u00e1in M Walsh A Rogers TR Unemo M Crowley B. 2015. Detailed characterization of the first high-level azithromycin-resistant Neisseria gonorrhoeae cases in Ireland. J Antimicrob Chemother 70: 2411\u20132413. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkv106"},{"key":"e_1_3_2_83_2","doi-asserted-by":"crossref","unstructured":"Starnino S Stefanelli P Neisseria gonorrhoeae Italian Study Group. 2009. Azithromycin-resistant Neisseria gonorrhoeae strains recently isolated in Italy. J Antimicrob Chemother 63: 1200\u20131204. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkp118"},{"key":"e_1_3_2_84_2","doi-asserted-by":"crossref","unstructured":"Unemo M Golparian D Hellmark B. 2013. First three Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Sweden: a threat to currently available dual-antimicrobial regimens for treatment of gonorrhea? Antimicrob Agents Chemother 58: 624\u2013625. [PubMed][CrossRef]","DOI":"10.1128\/AAC.02093-13"},{"key":"e_1_3_2_85_2","doi-asserted-by":"crossref","unstructured":"Stevens K Zaia A Tawil S Bates J Hicks V Whiley D Limnios A Lahra MM Howden BP. 2014. Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Australia. J Antimicrob Chemother 70: 1267\u20131268. [PubMed]","DOI":"10.1093\/jac\/dku490"},{"key":"e_1_3_2_86_2","doi-asserted-by":"crossref","unstructured":"Yuan LF Yin YP Dai XQ Pearline RV Xiang Z Unemo M Chen XS. 2011. Resistance to azithromycin of Neisseria gonorrhoeae isolates from 2 cities in China. Sex Transm Dis 38: 764\u2013768. [CrossRef]","DOI":"10.1097\/OLQ.0b013e318219cdb5"},{"key":"e_1_3_2_87_2","doi-asserted-by":"crossref","unstructured":"Galarza PG Abad R Canigia LF Buscemi L Pagano I Oviedo C V\u00e1zquez JA. 2010. New mutation in 23S rRNA gene associated with high level of azithromycin resistance in Neisseria gonorrhoeae . Antimicrob Agents Chemother 54: 1652\u20131653. [PubMed][CrossRef]","DOI":"10.1128\/AAC.01506-09"},{"key":"e_1_3_2_88_2","doi-asserted-by":"crossref","unstructured":"Katz AR Komeya AY Soge OO MKiaha MI Lee MV Wasserman GM Maningas EV Whelen AC Kirkcaldy RD Shapiro SJ Bolan GA Holmes KK. 2012. Neisseria gonorrhoeae with high-level resistance to azithromycin: case report of the first isolate identified in the United States. Clin Infect Dis 54: 841\u2013843. [PubMed][CrossRef]","DOI":"10.1093\/cid\/cir929"},{"key":"e_1_3_2_89_2","doi-asserted-by":"crossref","unstructured":"Allen VG Seah C Martin I Melano RG. 2014. Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae in Ontario Canada. Antimicrob Agents Chemother 58: 2528\u20132534. [PubMed][CrossRef]","DOI":"10.1128\/AAC.02608-13"},{"key":"e_1_3_2_90_2","doi-asserted-by":"crossref","unstructured":"Young H Moyes A McMillan A. 1997. Azithromycin and erythromycin resistant Neisseria gonorrhoeae following treatment with azithromycin. Int J STD AIDS 8: 299\u2013302. [PubMed][CrossRef]","DOI":"10.1258\/0956462971920127"},{"key":"e_1_3_2_91_2","doi-asserted-by":"crossref","unstructured":"Handsfield HH Dalu ZA Martin DH Douglas JM Jr McCarty JM Schlossberg D. 1994. Multicenter trial of single-dose azithromycin vs. ceftriaxone in the treatment of uncomplicated gonorrhea. Azithromycin Gonorrhea Study Group. Sex Transm Dis 21: 107\u2013111. [PubMed][CrossRef]","DOI":"10.1097\/00007435-199403000-00010"},{"key":"e_1_3_2_92_2","unstructured":"Workowski KA Bolan GA. 2015. Sexually transmitted diseases treatment guidelines 2015. MMWR Recommend Rep 64 (RR-03) : 1\u2013137. [PubMed]"},{"key":"e_1_3_2_93_2","doi-asserted-by":"crossref","unstructured":"Bignell C Fitzgerald M. 2011. UK national guideline for the management of gonorrhoea in adults 2011. Int J STD AIDS 22: 541\u2013547. [PubMed][CrossRef]","DOI":"10.1258\/ijsa.2011.011267"},{"key":"e_1_3_2_94_2","doi-asserted-by":"crossref","unstructured":"Newman LM Moran JS Workowski KA. 2007. Update on the management of gonorrhea in adults in the United States. Clin Infect Dis 44 (Suppl 3) : S84\u2013S101. [PubMed][CrossRef]","DOI":"10.1086\/511422"},{"key":"e_1_3_2_95_2","doi-asserted-by":"crossref","unstructured":"Barry PM Klausner JD. 2009. The use of cephalosporins for gonorrhea: the impending problem of resistance. Expert Opin Pharmacother 10: 555\u2013577. [PubMed][CrossRef]","DOI":"10.1517\/14656560902731993"},{"key":"e_1_3_2_96_2","doi-asserted-by":"crossref","unstructured":"Ison CA Mouton JW Jones K Fenton KA Livermore DM. 2004. Which cephalosporin for gonorrhoea? Sex Transm Infect 80: 386\u2013388. [PubMed][CrossRef]","DOI":"10.1136\/sti.2004.012757"},{"key":"e_1_3_2_97_2","doi-asserted-by":"crossref","unstructured":"Akasaka S Muratani T Yamada Y Inatomi H Takahashi K Matsumoto T. 2001. Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce beta-lactamase. J Infect Chemother 7: 49\u201350. [PubMed][CrossRef]","DOI":"10.1007\/s101560170034"},{"key":"e_1_3_2_98_2","doi-asserted-by":"crossref","unstructured":"Tanaka M Nakayama H Tunoe H Egashira T Kanayama A Saika T Kobayashi I Naito S. 2002. A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan. J Infect Chemother 8: 81\u201386. [PubMed][CrossRef]","DOI":"10.1007\/s101560200011"},{"key":"e_1_3_2_99_2","doi-asserted-by":"crossref","unstructured":"Chisholm SA Mouton JW Lewis DA Nichols T Ison CA Livermore DM. 2010. Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink? J Antimicrob Chemother 65: 2141\u20132148. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkq289"},{"key":"e_1_3_2_100_2","doi-asserted-by":"crossref","unstructured":"Deguchi T Yasuda M Yokoi S Ishida K Ito M Ishihara S Minamidate K Harada Y Tei K Kojima K Tamaki M Maeda S. 2003. Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval. J Infect Chemother 9: 35\u201339. [PubMed][CrossRef]","DOI":"10.1007\/s10156-002-0204-8"},{"key":"e_1_3_2_101_2","doi-asserted-by":"crossref","unstructured":"Ito M Yasuda M Yokoi S Ito S Takahashi Y Ishihara S Maeda S Deguchi T. 2004. Remarkable increase in central Japan in 2001\u20132002 of Neisseria gonorrhoeae isolates with decreased susceptibility to penicillin tetracycline oral cephalosporins and fluoroquinolones. Antimicrob Agents Chemother 48: 3185\u20133187. [PubMed][CrossRef]","DOI":"10.1128\/AAC.48.8.3185-3187.2004"},{"key":"e_1_3_2_102_2","doi-asserted-by":"crossref","unstructured":"Shimuta K Watanabe Y Nakayama S-I Morita-Ishihara T Kuroki T Unemo M Ohnishi M. 2015. Emergence and evolution of internationally disseminated cephalosporin-resistant Neisseria gonorrhoeae clones from 1995 to 2005 in Japan. BMC Infect Dis 15: 378. [PubMed][CrossRef]","DOI":"10.1186\/s12879-015-1110-x"},{"key":"e_1_3_2_103_2","doi-asserted-by":"crossref","unstructured":"Yokoi S Deguchi T Ozawa T Yasuda M Ito S Kubota Y Tamaki M Maeda S. 2007. Threat to cefixime treatment for gonorrhea. Emerg Infect Dis 13: 1275\u20131277. [PubMed]","DOI":"10.3201\/eid1308.060948"},{"key":"e_1_3_2_104_2","unstructured":"Japanese Society of Sexually Transmitted Infection. 2011. Gonococcal infection. Sexually transmitted infections diagnosis and treatment guidelines 2011. Jpn J Sex Transm Dis 22 (Suppl 1) : 52\u201359. (In Japanese.)"},{"key":"e_1_3_2_105_2","doi-asserted-by":"crossref","unstructured":"Cole MJ Spiteri G Jacobsson S Pitt R Grigorjev V Unemo M Euro-GASP Network. 2015. Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from the 2013 European surveillance. BMC Infect Dis 15: 321. [PubMed][CrossRef]","DOI":"10.1186\/s12879-015-1013-x"},{"key":"e_1_3_2_106_2","doi-asserted-by":"crossref","unstructured":"Hess D Wu A Golparian D Esmaili S Pandori W Sena E Klausner JD Barry P Unemo M Pandori M. 2012. Genome sequencing of a Neisseria gonorrhoeae isolate of a successful international clone with decreased susceptibility and resistance to extended-spectrum cephalosporins. Antimicrob Agents Chemother 56: 5633\u20135641. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00636-12"},{"key":"e_1_3_2_107_2","doi-asserted-by":"crossref","unstructured":"Li SY. 2012. Global transmission of multiple-drug resistant Neisseria gonorrhoeae strains refractive to cephalosporin treatment. J Formos Med Assoc 111: 463\u2013464. [PubMed][CrossRef]","DOI":"10.1016\/j.jfma.2012.03.004"},{"key":"e_1_3_2_108_2","doi-asserted-by":"crossref","unstructured":"Martin I Sawatzky P Allen V Hoang L Lefebvre B Mina N Wong T Gilmour M. 2012. Emergence and characterization of Neisseria gonorrhoeae isolates with decreased susceptibilities to ceftriaxone and cefixime in Canada: 2001\u20132010. Sex Transm Dis 39: 316\u2013323. [PubMed][CrossRef]","DOI":"10.1097\/OLQ.0b013e3182401b69"},{"key":"e_1_3_2_109_2","doi-asserted-by":"crossref","unstructured":"Su X Jiang F Qimuge Dai X Sun H Ye S. 2007. Surveillance of antimicrobial susceptibilities in Neisseria gonorrhoeae in Nanjing China 1999\u20132006. Sex Transm Dis 34: 995\u2013999. [CrossRef]","DOI":"10.1097\/OLQ.0b013e3180ca8f24"},{"key":"e_1_3_2_110_2","doi-asserted-by":"crossref","unstructured":"Shimuta K Unemo M Nakayama S Morita-Ishihara T Dorin M Kawahata T Ohnishi M. 2013. Antimicrobial resistance and molecular typing of Neisseria gonorrhoeae isolates in Kyoto and Osaka Japan 2010 to 2012: intensified surveillance after identification of the first strain (H041) with high-level ceftriaxone resistance. Antimicrob Agents Chemother 57: 5225\u20135232. [PubMed][CrossRef]","DOI":"10.1128\/AAC.01295-13"},{"key":"e_1_3_2_111_2","doi-asserted-by":"crossref","unstructured":"Ropp PA Hu M Olesky M Nicholas RA. 2002. Mutations in ponA the gene encoding penicillin-binding protein 1 and a novel locus penC are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae . Antimicrob Agents Chemother 46: 769\u2013777. [PubMed][CrossRef]","DOI":"10.1128\/AAC.46.3.769-777.2002"},{"key":"e_1_3_2_112_2","doi-asserted-by":"crossref","unstructured":"Zhao S Duncan M Tomberg J Davies C Unemo M Nicholas RA. 2009. Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae . Antimicrob Agents Chemother 53: 3744\u20133751. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00304-09"},{"key":"e_1_3_2_113_2","unstructured":"Public Health Agency of Canada. 2013. Canadian Guidelines on Sexually Transmitted Infections. Gonococcal Infections Chapter . Public Health Agency of Canada Ottawa Canada. http:\/\/www.phac-aspc.gc.ca\/std-mts\/sti-its\/cgsti-ldcits\/assets\/pdf\/section-5-6-eng.pdf. Accessed 22 November 2015."},{"key":"e_1_3_2_114_2","unstructured":"Australasian Sexual Health Alliance. Australian STI Management Guidelines for Use in Primary Care . Australasian Sexual Health Alliance Darlinghurst Australia. http:\/\/www.sti.guidelines.org.au\/sexually-transmissible-infections\/gonorrhoea#management. Accessed 22 November 2015."},{"key":"e_1_3_2_115_2","doi-asserted-by":"crossref","unstructured":"Chisholm SA Unemo M Quaye N Johansson E Cole MJ Ison CA Van de Laar MJ. 2013. Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone. Euro Surveill 18: pii=20358. [PubMed]","DOI":"10.2807\/ese.18.03.20358-en"},{"key":"e_1_3_2_116_2","doi-asserted-by":"crossref","unstructured":"Chisholm SA Quaye N Cole MJ Fredlund H Hoffmann S Jensen JS van de Laar MJ Unemo M Ison CA. 2011. An evaluation of gentamicin susceptibility of Neisseria gonorrhoeae isolates in Europe. J Antimicrob Chemother 66: 592\u2013595. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkq476"},{"key":"e_1_3_2_117_2","doi-asserted-by":"crossref","unstructured":"Cole M Unemo M Hoffmann S Chisholm SA Ison CA van de Laar MJ. 2011. The European gonococcal antimicrobial surveillance programme 2009. Euro Surveill 16: pii=19995. [PubMed]","DOI":"10.2807\/ese.16.42.19995-en"},{"key":"e_1_3_2_118_2","doi-asserted-by":"crossref","unstructured":"Ison CA Town K Obi C Chisholm S Hughes G Livermore DM Lowndes CM GRASP Collaborative Group. 2013. Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales 2007\u20132011. Lancet Infect Dis 13: 762\u2013768. [CrossRef]","DOI":"10.1016\/S1473-3099(13)70143-9"},{"key":"e_1_3_2_119_2","doi-asserted-by":"crossref","unstructured":"Kirkcaldy RD Hook EW III Soge OO del Rio C Kubin G Zenilman JM Papp JR. 2015. Trends in Neisseria gonorrhoeae susceptibility to cephalosporins in the United States 2006\u20132014. JAMA 314: 1869\u20131871. [PubMed][CrossRef]","DOI":"10.1001\/jama.2015.10347"},{"key":"e_1_3_2_120_2","doi-asserted-by":"crossref","unstructured":"Kirkcaldy RD Soge O Papp JR Hook EW III del Rio C Kubin G Weinstock HS. 2015. Analysis of Neisseria gonorrhoeae azithromycin susceptibility in the United States by the Gonococcal Isolate Surveillance Project 2005 to 2013. Antimicrob Agents Chemother 59: 998\u20131003. [PubMed][CrossRef]","DOI":"10.1128\/AAC.04337-14"},{"key":"e_1_3_2_121_2","doi-asserted-by":"crossref","unstructured":"Unemo M Shipitsyna E Domeika M. 2011. Gonorrhoea surveillance laboratory diagnosis and antimicrobial susceptibility testing of Neisseria gonorrhoeae in 11 countries of the eastern part of the WHO European region. APMIS 119: 643\u2013649. [PubMed][CrossRef]","DOI":"10.1111\/j.1600-0463.2011.02780.x"},{"key":"e_1_3_2_122_2","doi-asserted-by":"crossref","unstructured":"Goire N Lahra MM Chen M Donovan B Fairley CK Guy R Kaldor J Regan D Ward J Nissen MD Sloots TP Whiley DM. 2014. Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance. Nat Rev Microbiol 12: 223\u2013229. [PubMed][CrossRef]","DOI":"10.1038\/nrmicro3217"},{"key":"e_1_3_2_123_2","doi-asserted-by":"crossref","unstructured":"Schwarcz SK Zenilman JM Schnell D Knapp JS Hook EW III Thompson S Judson FN Holmes KK. 1990. National surveillance of antimicrobial resistance in Neisseria gonorrhoeae : the Gonococcal Isolate Surveillance Project. JAMA 264: 1413\u20131417. [PubMed][CrossRef]","DOI":"10.1001\/jama.264.11.1413"},{"key":"e_1_3_2_124_2","doi-asserted-by":"crossref","unstructured":"Fox KK del Rio C Holmes KK Hook EW III Judson FN Knapp JS Procop GW Wang SA Whittington WL Levine WC. 2001. Gonorrhea in the HIV era: a reversal in trends among men who have sex with men. Am J Public Health 91: 959\u2013964. [PubMed][CrossRef]","DOI":"10.2105\/AJPH.91.6.959"},{"key":"e_1_3_2_125_2","unstructured":"Centers for Disease Control and Prevention. 2007. Update to CDC\u2019s Sexually Transmitted Diseases Treatment Guidelines 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 56: 332\u2013336. [PubMed]"},{"key":"e_1_3_2_126_2","unstructured":"Workowski KA Berman S; Centers for Disease Control and Prevention. 2010. Sexually Transmitted Diseases Treatment Guidelines 2010. MMWR Recommend Rep 59 (RR-12) : 1\u2013110. [PubMed]"},{"key":"e_1_3_2_127_2","doi-asserted-by":"crossref","unstructured":"Centers for Disease Control and Prevention. 2012. Update to CDC\u2019s Sexually Transmitted Diseases Treatment Guidelines 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep 61: 590\u2013594. [PubMed]","DOI":"10.1016\/j.annemergmed.2012.10.014"},{"key":"e_1_3_2_128_2","unstructured":"World Health Organization. Strategies and Laboratory Methods for strengthening Surveillance of Sexually Transmitted Infections . World Health Organization Geneva Switzerland. http:\/\/apps.who.int\/iris\/bitstream\/10665\/75729\/1\/9789241504478_eng.pdf. Accessed 22 November 2015."},{"key":"e_1_3_2_129_2","unstructured":"Centers for Disease Control and Prevention. 1987. Antibiotic-resistant strains of Neisseria gonorrhoeae : policy guidelines for detection management and control. MMWR Morb Mortal Wkly Rep 36 (Suppl 5S) : 13S."},{"key":"e_1_3_2_130_2","doi-asserted-by":"crossref","unstructured":"Roy K Wang SA Meltzer MI. 2005. Optimizing treatment of antimicrobial-resistant Neisseria gonorrhoeae . Emerg Infect Dis 11: 1265\u20131273. [PubMed][CrossRef]","DOI":"10.3201\/eid1108.050157"},{"key":"e_1_3_2_131_2","doi-asserted-by":"crossref","unstructured":"Palmer HM Young H Winter A Dave J. 2008. Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother 62: 490\u2013494. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkn235"},{"key":"e_1_3_2_132_2","doi-asserted-by":"crossref","unstructured":"Kirkcaldy RD Weinstock HS Moore PC Philip SS Wiesenfeld HC Papp JR Kerndt PR Johnson S Ghanem KG Hook EW III. 2014. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis 59: 1083\u20131091. [PubMed][CrossRef]","DOI":"10.1093\/cid\/ciu521"},{"key":"e_1_3_2_133_2","doi-asserted-by":"crossref","unstructured":"Lee H Hong SG Soe Y Yong D Jeong SH Lee K Chong Y. 2011. Trends in antimicrobial resistance of Neisseria gonorrhoeae isolated from Korean patients from 2000 to 2006. Sex Transm Dis 38: 1082\u20131086. [PubMed][CrossRef]","DOI":"10.1097\/OLQ.0b013e31822e60a4"},{"key":"e_1_3_2_134_2","doi-asserted-by":"crossref","unstructured":"Olsen B Pham TL Golparian D Johansson E Tran HK Unemo M. 2013. Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam 2011. BMC Infect Dis 13: 40. [PubMed][CrossRef]","DOI":"10.1186\/1471-2334-13-40"},{"key":"e_1_3_2_135_2","doi-asserted-by":"crossref","unstructured":"Quaye N Cole MJ Ison CA. 2014. Evaluation of the activity of ertapenem against gonococcal isolates exhibiting a range of susceptibilities to cefixime. J Antimicrob Chemother 69: 1568\u20131571. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dkt537"},{"key":"e_1_3_2_136_2","doi-asserted-by":"crossref","unstructured":"Unemo M Golparian D Limnios A Whiley D Ohnishi M Lahra MM Tapsall JW. 2012. In vitro activity of ertapenem vs. ceftriaxone against Neisseria gonorrhoeae isolates with highly diverse ceftriaxone MIC values and effects of ceftriaxone resistance determinants\u2014ertapenem for treatment of gonorrhea? Antimicrob Agents Chemother 56: 3603\u20133609. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00326-12"},{"key":"e_1_3_2_137_2","doi-asserted-by":"crossref","unstructured":"Hauser C Hirzberger L Unemo M Furrer H Endimiani A. 2015. In vitro activity of fosfomycin alone and in combination with ceftriaxone or azithromycin against clinical Neisseria gonorrhoeae isolates. Antimicrob Agents Chemother 59: 1605\u20131611. [PubMed][CrossRef]","DOI":"10.1128\/AAC.04536-14"},{"key":"e_1_3_2_138_2","doi-asserted-by":"crossref","unstructured":"Brown LB Krysiak R Kamanga G Mapanje C Kanyamula H Banda B Mhango C Hoffman M Kamwendo D Hobbs M Hosseinipour MC Martinson F Cohen MS Hoffman IF. 2010. Neisseria gonorrhoeae antimicrobial susceptibility in Lilongwe Malawi 2007. Sex Transm Dis 37: 169\u2013172. [PubMed][CrossRef]","DOI":"10.1097\/OLQ.0b013e3181bf575c"},{"key":"e_1_3_2_139_2","doi-asserted-by":"crossref","unstructured":"Ross JD Lewis DA. 2012. Cephalosporin resistant Neisseria gonorrhoeae : time to consider gentamicin? Sex Transm Infect 88: 6\u20138. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2011-050362"},{"key":"e_1_3_2_140_2","doi-asserted-by":"crossref","unstructured":"Hathorn E Dhasmana D Duley L Ross JD. 2014. The effectiveness of gentamicin in the treatment of Neisseria gonorrhoeae : a systematic review. Syst Rev 3: 104. [PubMed][CrossRef]","DOI":"10.1186\/2046-4053-3-104"},{"key":"e_1_3_2_141_2","doi-asserted-by":"crossref","unstructured":"Dowell D Kirkcaldy RD. 2013. Effectiveness of gentamicin for gonorrhoea treatment: systematic review and meta-analysis. Sex Transm Infect 89: 142\u2013147. [CrossRef]","DOI":"10.1136\/postgradmedj-2012-050604rep"},{"key":"e_1_3_2_142_2","doi-asserted-by":"crossref","unstructured":"Biedenbach DJ Turner LL Jones RN Farell DJ. 2012. Activity of JNJ-Q2 a novel fluoroquinolone tested against Neisseria gonorrhoeae including ciprofloxacin-resistant strains. Diagn Microbiol Infect Dis 74: 204\u2013206. [PubMed][CrossRef]","DOI":"10.1016\/j.diagmicrobio.2012.06.006"},{"key":"e_1_3_2_143_2","unstructured":"Roberts MC Remy JM Longcor JD Marra A Sun E Duffy EM. 2013. In vitro activity of delafloxacin against Neisseria gonorrhoeae clinical isolates. STI & AIDS World Congress 2013 14 to 17 July 2013 Vienna Austria poster P2.197."},{"key":"e_1_3_2_144_2","doi-asserted-by":"crossref","unstructured":"Hamasuna R Yasuda M Ishikawa K Uehara S Hayami H Takahashi S Matsumoto T Yamamoto S Minamitani S Watanabe A Iwata S Kaku M Kadota J Sunakawa K Sato J Hanaki H Tsukamoto T Kiyota H Egawa S Tanaka K Arakawa S Fujisawa M Kumon H Kobayashi K Matsubara A Naito S Kuroiwa K Hirayama H Narita H Hosobe T Ito S Ito K Kawai S Ito M Chokyu H Matsumura M Yoshioka M Uno S Monden K Takayama K Kaji S Kawahara M Sumii T Kadena H Yamaguchi T Maeda S Nishi S Nishimura H Shirane T Yoh M Akiyama K Imai T Kano M. 2015. The second nationwide surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae from male urethritis in Japan 2012-2013. J Infect Chemother 21: 340\u2013345. [PubMed][CrossRef]","DOI":"10.1016\/j.jiac.2015.01.010"},{"key":"e_1_3_2_145_2","doi-asserted-by":"crossref","unstructured":"Kazamori D Aoi H Sugimoto K Ueshima T Amano H Itoh K Kuramoto Y Yazaki A. 2014. In vitro activity of WQ-3810 a novel fluoroquinolone against multidrug-resistant and fluoroquinolone-resistant pathogens. Int J Antimicrob Agents 44: 443\u2013449. [PubMed][CrossRef]","DOI":"10.1016\/j.ijantimicag.2014.07.017"},{"key":"e_1_3_2_146_2","unstructured":"Kerstein K Fyfe C Sutcliffe JA Grossman TH. 2013. Eravacycline (TP-434) is active against susceptible and multidrug-resistant Neisseria gonorrhoeae poster E-1181. Abstr 53rd Intersci Conf Antimicrob Agents Chemother 10 to 13 September 2013 Denver CO."},{"key":"e_1_3_2_147_2","doi-asserted-by":"crossref","unstructured":"Zhang YY Zhou L Zhu DM Wu PC Hu FP Wu WH Wang F. 2004. In vitro activities of tigecycline against clinical isolates from Shanghai China. Diagn Microbiol Infect Dis 50: 267\u2013281. [PubMed][CrossRef]","DOI":"10.1016\/j.diagmicrobio.2004.08.007"},{"key":"e_1_3_2_148_2","doi-asserted-by":"crossref","unstructured":"Fujimoto K Takemoto K Hatano K Nakai T Terashita S Matsumoto M Eriguchi Y Eguchi K Shimizudani T Sato K Kanazawa K Sunagawa M Ueda Y. 2013. Novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals. Antimicrob Agents Chemother 57: 697\u2013707. [PubMed][CrossRef]","DOI":"10.1128\/AAC.01051-12"},{"key":"e_1_3_2_149_2","doi-asserted-by":"crossref","unstructured":"Jacobsson S Golparian D Phan LT Ohnishi M Fredlund H Or YS Unemo M. 2015. In vitro activities of the novel bicyclolides modithromycin (EDP-420 EP-013420 S-013420) and EDP-322 against MDR clinical Neisseria gonorrhoeae isolates and international reference strains. J Antimicrob Chemother 70: 173\u2013177. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dku344"},{"key":"e_1_3_2_150_2","doi-asserted-by":"crossref","unstructured":"Golparian D Fernandes P Ohnishi M Jensen JS Unemo M. 2012. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against a large collection of clinical Neisseria gonorrhoeae isolates and international reference strains including those with various high-level antimicrobial resistance\u2014potential treatment option for gonorrhea? Antimicrob Agents Chemother 56: 2739\u20132742. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00036-12"},{"key":"e_1_3_2_151_2","unstructured":"Koeth LM Fisher. 2013. In vitro activity of dalbavancin against Neisseria gonorrhoeae and development of a broth microdilution method poster 255. IDWeek 2013 2 to 6 October 2013 San Francisco CA."},{"key":"e_1_3_2_152_2","doi-asserted-by":"crossref","unstructured":"Hook EW III Golden M Jamieson BD Dixon PB Harbison HS Lowens S Fernandes P. 2015. A phase 2 trial of oral solithromycin 1200 mg or 1000 mg as single-dose oral therapy for uncomplicated gonorrhea. Clin Infect Dis 61: 1043\u20131048. [PubMed][CrossRef]","DOI":"10.1093\/cid\/civ478"},{"key":"e_1_3_2_153_2","unstructured":"Paukner S Gruss A Fritsche TR Ivezic-Schoenfeld Z Jones RN. 2013. In vitro activity of the novel pleuromutilin BC-3781 tested against bacterial pathogens causing sexually transmitted diseases (STD) poster E-1183. Abstr 53rd Intersci Conf Antimicrob Agents Chemother 10 to 13 September 2013 Denver CO."},{"key":"e_1_3_2_154_2","unstructured":"Bouchillon SK Hoban DJ Hackel MA Butler DL Memarsh P Alley MRK. 2010. In vitro activities of AN3365: a novel boron containing protein synthesis inhibitor and other antimicrobial agents against anaerobes and Neisseria gonorrhoeae poster F1-1640. 50th Intersci Conf Antimicrob Agents Chemother 12 to 15 September 2010 Boston MA."},{"key":"e_1_3_2_155_2","unstructured":"Swanson S Lee CJ Liang X Toone E Zhou P Nicholas R. 2012. LpxC inhibitors as novel therapeutics for treatment of antibiotic-resistant Neisseria gonorrhoeae . 18th Int Pathog Neisseria Conf 9 to 14 September 2012 Wurzburg Germany poster p174."},{"key":"e_1_3_2_156_2","doi-asserted-by":"crossref","unstructured":"Escaich S Prouvensier L Saccomani M Durant L Oxoby M Gerusz V Moreau F Vongsouthi V Maher K Morrissey I Soulama-Mouze C. 2011. The MUT056399 inhibitor of FabI is a new antistaphylococcal compound. Antimicrob Agents Chemother 55: 4692\u20134697. [PubMed][CrossRef]","DOI":"10.1128\/AAC.01248-10"},{"key":"e_1_3_2_157_2","doi-asserted-by":"crossref","unstructured":"Jeverica S Golparian D Hanzelka B Fowlie AJ Maticic M Unemo M. 2014. High in vitro activity of a novel dual bacterial topoisomerase inhibitor of the ATPase activities of GyrB and ParE (VT12-008911) against Neisseria gonorrhoeae isolates with various high-level antimicrobial resistance and multidrug resistance. J Antimicrob Chemother 69: 1866\u20131872. [PubMed][CrossRef]","DOI":"10.1093\/jac\/dku073"},{"key":"e_1_3_2_158_2","doi-asserted-by":"crossref","unstructured":"Jacobsson S Golparian D Alm RA Huband M Mueller J Jensen JS Ohnishi M Unemo M. 2014. High in vitro activity of the novel spiropyrimidinetrione AZD0914 a DNA gyrase inhibitor against multidrug resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea. Antimicrob Agents Chemother 58: 5585\u20135588. [PubMed][CrossRef]","DOI":"10.1128\/AAC.03090-14"},{"key":"e_1_3_2_159_2","doi-asserted-by":"crossref","unstructured":"Huband MD Bradford PA Otterson LG Basarab GS Kutschke A Giacobbe R Patey SA Alm RA Johnstone MR Potter ME Miller PF Mueller JP. 2015. In vitro antibacterial activity of AZD0914: a new spiropyrimidinetrione DNA gyrase\/topoisomerase inhibitor with potent activity against Gram-positive fastidious Gram-negative and atypical bacteria. Antimicrob Agents Chemother 59: 467\u2013474. [PubMed][CrossRef]","DOI":"10.1128\/AAC.04124-14"},{"key":"e_1_3_2_160_2","doi-asserted-by":"crossref","unstructured":"Unemo M Ringlander J Wiggins C Fredlund H Jacobsson S Cole M the European Collaborative Group. 2015. High in vitro susceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical Neisseria gonorrhoeae isolates in 21 European countries from 2012 to 2014. Antimicrob Agents Chemother 59: 5220\u20135225. [PubMed][CrossRef]","DOI":"10.1128\/AAC.00786-15"},{"key":"e_1_3_2_161_2","doi-asserted-by":"crossref","unstructured":"Alm RA Lahiri SD Kutschke A Otterson LG McLaughlin RE Whiteaker JD Lewis LA Su X Huband MD Gardner H Mueller JP. 2015. Characterization of the novel DNA gyrase inhibitor AZD0914: low resistance potential and lack of cross-resistance in Neisseria gonorrhoeae . Antimicrob Agents Chemother 59: 1478\u20131486. [PubMed][CrossRef]","DOI":"10.1128\/AAC.04456-14"},{"key":"e_1_3_2_162_2","doi-asserted-by":"crossref","unstructured":"Jerse AE Deal CD. 2013. Vaccine research for gonococcal infections: where are we? Sex Transm Infect 89 (Suppl 4) : iv63\u2013iv68. [PubMed][CrossRef]","DOI":"10.1136\/sextrans-2013-051225"},{"key":"e_1_3_2_163_2","doi-asserted-by":"crossref","unstructured":"Grad YH Kirkcaldy RD Trees D Dordel J Harris SR Goldstein E Weinstock H Parkhill J Hanage WP Bentley S Lipsitch M. 2014. Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect Dis 14: 220\u2013226. [CrossRef]","DOI":"10.1016\/S1473-3099(13)70693-5"},{"key":"e_1_3_2_164_2","doi-asserted-by":"crossref","unstructured":"Ohnishi M Unemo M. 2014. Phylogenomics for drug-resistant Neisseria gonorrhoeae . Lancet Infect Dis 14: 179\u2013180. [CrossRef]","DOI":"10.1016\/S1473-3099(13)70700-X"},{"key":"e_1_3_2_165_2","doi-asserted-by":"crossref","unstructured":"Baarda BI Sikora AE. 2015. Proteomics of Neisseria gonorrhoeae : the treasure hunt for countermeasures against an old disease. Front Microbiol 6: 1190. [PubMed][CrossRef]","DOI":"10.3389\/fmicb.2015.01190"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/microbiolspec.EI10-0009-2015","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/microbiolspec.EI10-0009-2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T21:43:42Z","timestamp":1748987022000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/microbiolspec.EI10-0009-2015"}},"subtitle":[],"editor":[{"given":"W. Michael","family":"Scheld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"James M.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Richard J.","family":"Whitley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,5,6]]},"references-count":164,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,5,6]]}},"alternative-id":["10.1128\/microbiolspec.EI10-0009-2015"],"URL":"https:\/\/doi.org\/10.1128\/microbiolspec.ei10-0009-2015","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,6]]},"assertion":[{"value":"2015-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"4.3.35"}}