Research article Open Access
Like 0


Resistance of to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted.


Article metrics loading...

Loading full text...

Full text loading...



  1. Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev. 2014;27(3):587-613.  https://doi.org/10.1128/CMR.00010-14  PMID: 24982323 
  2. Ison CA, Hussey J, Sankar KN, Evans J, Alexander S. Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010. Euro Surveill. 2011;16(14):19833. PMID: 21492528 
  3. de Vries HJC, van der Helm JJ, Schim van der Loeff MF, van Dam AP. Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility is increasingly common in men who have sex with men, Amsterdam, the Netherlands. Euro Surveill. 2009;14(37):19330. PMID: 19761737 
  4. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. PMID: 26042815 
  5. Bignell C, Unemo M, European STI Guidelines Editorial Board. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS. 2013;24(2):85-92.  https://doi.org/10.1177/0956462412472837  PMID: 24400344 
  6. World Health Organization. WHO guidelines for the treatment of Neisseria gonorrhoeae. Geneva: WHO, 2016.
  7. Bercot B, Belkacem A, Goubard A, Mougari F, Sednaoui P, La Ruche G, et al. High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014. Euro Surveill. 2014;19(44):20951.  https://doi.org/10.2807/1560-7917.ES2014.19.44.20951  PMID: 25394255 
  8. Cao WL, Liang JY, Li XD, Bi C, Yang RD, Liang YH, et al. Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated from Guangzhou, China, 2000 to 2005 and 2008 to 2013. Sex Transm Dis. 2015;42(1):27-9.  https://doi.org/10.1097/OLQ.0000000000000218  PMID: 25504297 
  9. Chisholm SA, Wilson J, Alexander S, Tripodo F, Al-Shahib A, Schaefer U, et al. An outbreak of high-level azithromycin resistant Neisseria gonorrhoeae in England. Sex Transm Infect. 2016;92(5):365-7.  https://doi.org/10.1136/sextrans-2015-052312  PMID: 26601852 
  10. Deguchi T, Yasuda M, Hatazaki K, Kameyama K, Horie K, Kato T, et al. New Clinical Strain of Neisseria gonorrhoeae with Decreased Susceptibility to Ceftriaxone, Japan. Emerg Infect Dis. 2016;22(1):142-4.  https://doi.org/10.3201/eid2201.150868  PMID: 26689442 
  11. Gose SO, Soge OO, Beebe JL, Nguyen D, Stoltey JE, Bauer HM. Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by high-level resistance in California. Sex Transm Dis. 2015;42(5):279-80.  https://doi.org/10.1097/OLQ.0000000000000265  PMID: 25868141 
  12. Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S, Iwasaku K, et al. 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. 2011;55(7):3538-45.  https://doi.org/10.1128/AAC.00325-11  PMID: 21576437 
  13. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother. 2012;56(3):1273-80.  https://doi.org/10.1128/AAC.05760-11  PMID: 22155830 
  14. Fifer H, Natarajan U, Jones L, Alexander S, Hughes G, Golparian D, et al. Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea. N Engl J Med. 2016;374(25):2504-6.  https://doi.org/10.1056/NEJMc1512757  PMID: 27332921 
  15. Workowski KA, Berman SM, Douglas JM Jr. Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. Ann Intern Med. 2008;148(8):606-13.  https://doi.org/10.7326/0003-4819-148-8-200804150-00005  PMID: 18413622 
  16. van den Broek S, van Rooijen MS, van Veen M, Hogewoning A. Jaarverslag 2014, Soa-polikliniek. Amsterdam: GGD Amsterdam, 2015. Dutch
  17. de Vries HJC, van Doornum GJJ, Bax CJ. Multidisciplinaire Richtlijn Seksueel Overdraagbare Aandoeningen voor de 2e Lijn. Bilthoven: Nederlandse Vereniging voor Dermatologie en Venereologie, 2012. Dutch
  18. Wind CM, de Vries HJC, Schim van der Loeff MF, Unemo M, van Dam AP. Successful Combination of Nucleic Acid Amplification Test Diagnostics and Targeted Deferred Neisseria gonorrhoeae Culture. J Clin Microbiol. 2015;53(6):1884-90.  https://doi.org/10.1128/JCM.00369-15  PMID: 25832300 
  19. European Committee on Antimicrobial Susceptibility Testing. Breakpoint table for interpretation of MICs and zone diameters, version 6.0. Stockholm: EUCAST, 2016. (last updated: 20 January 2016)
  20. European Centre for Disease Prevention and Control. Gonococcal antimicrobial susceptibility surveillance in Europe, 2013. Stockholm: ECDC, 2015.
  21. Lebedzeu F, Golparian D, Titov L, Pankratava N, Glazkova S, Shimanskaya I, et al. Antimicrobial susceptibility/resistance and NG-MAST characterisation of Neisseria gonorrhoeae in Belarus, Eastern Europe, 2010-2013. BMC Infect Dis. 2015;15(1):29.  https://doi.org/10.1186/s12879-015-0755-9  PMID: 25637258 
  22. Ison CA, Town K, Obi C, Chisholm S, Hughes G, Livermore DM, et al. , GRASP collaborative group. Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis. 2013;13(9):762-8.  https://doi.org/10.1016/S1473-3099(13)70143-9  PMID: 23764300 
  23. Kirkcaldy RD, Hook EW 3rd, Soge OO, del Rio C, Kubin G, Zenilman JM, et al. Trends in Neisseria gonorrhoeae Susceptibility to Cephalosporins in the United States, 2006-2014. JAMA. 2015;314(17):1869-71.  https://doi.org/10.1001/jama.2015.10347  PMID: 26529166 
  24. Heymans R, Bruisten SM, Golparian D, Unemo M, de Vries HJC, van Dam AP. Clonally related Neisseria gonorrhoeae isolates with decreased susceptibility to the extended-spectrum cephalosporin cefotaxime in Amsterdam, the Netherlands. Antimicrob Agents Chemother. 2012;56(3):1516-22.  https://doi.org/10.1128/AAC.05481-11  PMID: 22214779 
  25. van Dam AP, van Ogtrop ML, Golparian D, Mehrtens J, de Vries HJC, Unemo M. Verified clinical failure with cefotaxime 1g for treatment of gonorrhoea in the Netherlands: a case report. Sex Transm Infect. 2014;90(7):513-4.  https://doi.org/10.1136/sextrans-2014-051552  PMID: 25114322 
  26. Town K, Lowndes CM, Hughes G, Obi C, Chisholm S, Ison CA, GRASP collaborative group. Can previous first-line therapies for Neisseria gonorrhoeae be targeted to specific patient subgroups to treat gonorrhea? Sex Transm Dis. 2015;42(1):37-42.  https://doi.org/10.1097/OLQ.0000000000000223  PMID: 25504299 
  27. Olsen B, Lan PT, Golparian D, Johansson E, Khang TH, Unemo M. Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam, 2011. BMC Infect Dis. 2013;13(1):40.  https://doi.org/10.1186/1471-2334-13-40  PMID: 23351067 
  28. Cole MJ, Spiteri G, Jacobsson S, Pitt R, Grigorjev V, Unemo M, Euro-GASP Network. Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from the 2013 European surveillance. BMC Infect Dis. 2015;15(1):321.  https://doi.org/10.1186/s12879-015-1013-x  PMID: 26259560 
  29. Fingerhuth SM, Bonhoeffer S, Low N, Althaus CL. Antibiotic-Resistant Neisseria gonorrhoeae Spread Faster with More Treatment, Not More Sexual Partners. PLoS Pathog. 2016;12(5):e1005611.  https://doi.org/10.1371/journal.ppat.1005611  PMID: 27196299 
  30. Soge OO, Harger D, Schafer S, Toevs K, Raisler KA, Venator K, et al. Emergence of increased azithromycin resistance during unsuccessful treatment of Neisseria gonorrhoeae infection with azithromycin (Portland, OR, 2011). Sex Transm Dis. 2012;39(11):877-9.  https://doi.org/10.1097/OLQ.0b013e3182685d2b  PMID: 23064537 
  31. Cole MJ, Spiteri G, Town K, Unemo M, Hoffmann S, Chisholm SA, et al. , Euro-GASP Network. Risk factors for antimicrobial-resistant Neisseria gonorrhoeae in Europe. Sex Transm Dis. 2014;41(12):723-9.  https://doi.org/10.1097/OLQ.0000000000000185  PMID: 25581808 
  32. La Ruche G, Goubard A, Bercot B, Cambau E, Semaille C, Sednaoui P. Gonococcal infections and emergence of gonococcal decreased susceptibility to cephalosporins in France, 2001 to 2012. Euro Surveill. 2014;19(34):20885.  https://doi.org/10.2807/1560-7917.ES2014.19.34.20885  PMID: 25188611 
  33. Bissessor M, Whiley DM, Lee DM, Snow AF, Fairley CK, Peel J, et al. Detection of Neisseria gonorrhoeae Isolates from Tonsils and Posterior Oropharynx. J Clin Microbiol. 2015;53(11):3624-6.  https://doi.org/10.1128/JCM.01647-15  PMID: 26292303 
  34. Bolan GA, Sparling PF, Wasserheit JN. The emerging threat of untreatable gonococcal infection. N Engl J Med. 2012;366(6):485-7.  https://doi.org/10.1056/NEJMp1112456  PMID: 22316442 
  35. Trecker MA, Waldner C, Jolly A, Liao M, Gu W, Dillon JA. Behavioral and socioeconomic risk factors associated with probable resistance to ceftriaxone and resistance to penicillin and tetracycline in Neisseria gonorrhoeae in Shanghai. PLoS One. 2014;9(2):e89458.  https://doi.org/10.1371/journal.pone.0089458  PMID: 24586792 
  36. Goldstein E, Kirkcaldy RD, Reshef D, Berman S, Weinstock H, Sabeti P, et al. Factors related to increasing prevalence of resistance to ciprofloxacin and other antimicrobial drugs in Neisseria gonorrhoeae, United States. Emerg Infect Dis. 2012;18(8):1290-7.  https://doi.org/10.3201/eid1808.111202  PMID: 22840274 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error