Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium

Nature Reviews Urology volume 14, pages 139–152 (2017)Cite this article

Subjects

Key Points

  • The burden of Neisseria gonorrhoeae and Mycoplasma genitalium infections and multidrug-resistance in the aetiological agents are major global public health concerns that are poorly surveyed and controlled

  • N. gonorrhoeae and M. genitalium are evolving into so-called superbugs; infections with these bacteria have become exceedingly difficult to treat and they might become untreatable in certain circumstances

  • Current dual antimicrobial therapy for gonorrhoea (ceftriaxone plus azithromycin) should be considered in all settings where regular, local and quality-assured antimicrobial resistance (AMR) data do not support other therapeutic options

  • Dual antimicrobial therapy might also need to be considered for M. genitalium infections

  • Development of novel antimicrobials and treatment algorithms that emphasizes dual antimicrobial therapy and AMR testing is imperative to minimize AMR emergence, enhance AMR surveillance and, ideally, guide personalized treatment

  • Some newly developed antimicrobials, for example the fluoroketolide solithromycin, the spiropyrimidinetrione zoliflodacin and the pleuromutilin lefamulin, need further evaluation in clinical trials as potential future treatments of gonorrhoea and M. genitalium infections

Abstract

The emergence of antimicrobial resistance (AMR) is a major concern worldwide and already compromises treatment effectiveness and control of several bacterial sexually transmitted infections (STIs). Neisseria gonorrhoeae and Mycoplasma genitalium are evolving into so-called superbugs that can become resistant, both in vitro and clinically, to essentially all antimicrobials available for treatment, causing exceedingly difficult-to-treat or untreatable STIs and threatening global public health. Widespread AMR in these bacteria is likely to persist and even worsen in the future, owing to the high number of infections, widespread and uncontrolled use of antimicrobials, limited surveillance of AMR and clinical failures, as well as the extraordinary capacity of these bacteria to develop AMR. This development would not only result in an increased prevalence of N. gonorrhoeae and M. genitalium infections but also in a considerably increasing number of severe complications affecting reproductive health. To combat this threat, clinicians need to be aware of the current guidelines on diagnostic procedures, recommended treatment regimens, as well as therapeutic options for multidrug-resistant bacteria. AMR testing needs to be more frequently performed, inform treatment decisions and elucidate how AMRs compromise treatment effectiveness, guiding research for effective future therapies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Antimicrobial therapy of uncomplicated Mycoplasma genitalium infections.

Similar content being viewed by others

References

  1. Newman, L. et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS ONE 10, e0143304 (2015).

    PubMed  PubMed Central  Google Scholar 

  2. Jensen, J. S., Cusini, M., Gomberg, M. & Moi, H. 2016 European guideline on Mycoplasma genitalium infections. J. Eur. Acad. Dermatol. Venereol. 30, 1650–1656 (2016).

    CAS  PubMed  Google Scholar 

  3. Taylor-Robinson, D. & Jensen, J. S. Mycoplasma genitalium: from Chrysalis to multicolored butterfly. Clin. Microbiol. Rev. 24, 498–514 (2011).

    PubMed  PubMed Central  Google Scholar 

  4. World Health Organization. Global Action Plan to Control the Spread and Impact of Antimicrobial Resistance in Neisseria gonorrhoeae (WHO, 2012).

  5. Unemo, M. & Shafer, W. M. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st Century: past, evolution, and future. Clin. Microbiol. Rev. 27, 587–613 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Unemo, M. & Nicholas, R. A. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 7, 1401–1422 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Unemo, M. Current and future antimicrobial treatment of gonorrhoea — the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infect. Dis. 15, 364 (2015).

    PubMed  PubMed Central  Google Scholar 

  8. Ison, C. A., Deal, C. & Unemo, M. Current and future treatment options for gonorrhoea. Sex. Transm. Infect. 89 (Suppl. 4), iv52–iv56 (2013).

    PubMed  Google Scholar 

  9. Bignell, C. & Unemo, M. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int. J. STD AIDS 24, 85–92 (2013).

    CAS  PubMed  Google Scholar 

  10. Workowski, K. A. & Bolan, G. A. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm. Rep. 64, 1–137 (2015).

    PubMed  PubMed Central  Google Scholar 

  11. Public Health Agency of Canada. Canadian Guidelines on Sexually Transmitted Infections. Gonococcal Infections Chapter (Public Health Agency of Canada, 2013).

  12. Australasian Sexual Health Alliance. Australian STI management guidelines for use in primary care. ASHA www.sti.guidelines.org.au/sexually-transmissible-infections/gonorrhoea#management (2016).

  13. Manhart, L. E. et al. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin. Infect. Dis. 56, 934–942 (2013).

    CAS  PubMed  Google Scholar 

  14. Mena, L. A., Mroczkowski, T. F., Nsuami, M. & Martin, D. H. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men. Clin. Infect. Dis. 48, 1649–1654 (2009).

    CAS  PubMed  Google Scholar 

  15. Salado-Rasmussen, K. & Jensen, J. S. Mycoplasma genitalium testing pattern and macrolide resistance: a Danish nationwide retrospective survey. Clin. Infect. Dis. 59, 24–30 (2014).

    PubMed  PubMed Central  Google Scholar 

  16. Anagrius, C., Lore, B. & Jensen, J. S. Treatment of Mycoplasma genitalium. Observations from a Swedish STD clinic. PLoS ONE 8, e61481 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Schwebke, J. R. et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens — a randomized clinical trial. Clin. Infect. Dis. 52, 163–170 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Jernberg, E., Moghaddam, A. & Moi, H. Azithromycin and moxifloxacin for microbiological cure of Mycoplasma genitalium infection: an open study. Int. J. STD AIDS 19, 676–679 (2008).

    CAS  PubMed  Google Scholar 

  19. Couldwell, D. L., Tagg, K. A., Jeoffreys, N. J. & Gilbert, G. L. Failure of moxifloxacin treatment in Mycoplasma genitalium infections due to macrolide and fluoroquinolone resistance. Int. J. STD AIDS 24, 822–828 (2013).

    PubMed  Google Scholar 

  20. Manhart, L. E. et al. Treatment outcomes for persistent Mycoplasma genitalium associated NGU: evidence of moxifloxacin treatment failures [abstract O02.3]. Sex. Transm. Infect. 89 (Suppl. 1), A29 (2013).

    Google Scholar 

  21. Lanjouw, E. et al. Background review for the '2015 European guideline on the management of Chlamydia trachomatis infections'. Int. J. STD AIDS 2015, 0956462415618838 (2015).

    Google Scholar 

  22. Nwokolo, N. C. et al. 2015 UK national guideline for the management of infection with Chlamydia trachomatis. Int. J. STD AIDS 27, 251–267 (2016).

    PubMed  Google Scholar 

  23. Horner, P. J. Azithromycin antimicrobial resistance and genital Chlamydia trachomatis infection: duration of therapy may be the key to improving efficacy. Sex. Transm. Infect. 88, 154–156 (2012).

    PubMed  Google Scholar 

  24. Sandoz, K. M. & Rockey, D. D. Antibiotic resistance in Chlamydiae. Future Microbiol. 5, 1427–1442 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang, S. A. et al. Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J. Infect. Dis. 191, 917–923 (2005).

    PubMed  Google Scholar 

  26. O'Neill, C. E. et al. Chlamydia trachomatis clinical isolates identified as tetracycline resistant do not exhibit resistance in vitro: whole-genome sequencing reveals a mutation in porB but no evidence for tetracycline resistance genes. Microbiology 159, 748–756 (2013).

    CAS  PubMed  Google Scholar 

  27. Handsfield, H. H. Questioning azithromycin for chlamydial infection. Sex. Transm. Dis. 38, 1028–1029 (2011).

    PubMed  Google Scholar 

  28. Sena, A. C. et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections in men with nongonococcal urethritis: predictors and persistence after therapy. J. Infect. Dis. 206, 357–365 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kong, F. Y. & Hocking, J. S. Treatment challenges for urogenital and anorectal Chlamydia trachomatis. BMC Infect. Dis. 15, 293 (2015).

    PubMed  PubMed Central  Google Scholar 

  30. Somani, J., Bhullar, V. B., Workowski, K. A., Farshy, C. E. & Black, C. M. Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure. J. Infect. Dis. 181, 1421–1427 (2000).

    CAS  PubMed  Google Scholar 

  31. Bhengraj, A. R., Srivastava, P. & Mittal, A. Lack of mutation in macrolide resistance genes in Chlamydia trachomatis clinical isolates with decreased susceptibility to azithromycin. Int. J. Antimicrob. Agents 38, 178–179 (2011).

    CAS  PubMed  Google Scholar 

  32. Mpiga, P. & Ravaoarinoro, M. Effects of sustained antibiotic bactericidal treatment on Chlamydia trachomatis-infected epithelial-like cells (HeLa) and monocyte-like cells (THP-1 and U-937). Int. J. Antimicrob. Agents 27, 316–324 (2006).

    CAS  PubMed  Google Scholar 

  33. Unemo, M., Endre, K. M. A. & Moi, H. The five days azithromycin treatment regimen (500 mg×1, 250 mg×4) used for Mycoplasma genitalium infections also effectively eradicates Chlamydia trachomatis. Acta Derm. Venereol. 95, 730–732 (2015).

    CAS  PubMed  Google Scholar 

  34. Horner, P. J., Blee, K., Falk, L., van der Meijden, W. & Moi, H. 2016 European guideline on the management of non-gonococcal urethritis. Int. J. STD AIDS 27, 928–937 (2016).

    CAS  PubMed  Google Scholar 

  35. Janier, M. et al. 2014 European guideline on the management of syphilis. J. Eur. Acad. Dermatol. Venereol. 28, 1581–1593 (2014).

    CAS  PubMed  Google Scholar 

  36. Stamm, L. V. Syphilis: antibiotic treatment and resistance. Epidemiol. Infect. 143, 1567–1574 (2015).

    CAS  PubMed  Google Scholar 

  37. Tipple, C. & Taylor, G. P. Syphilis testing, typing, and treatment follow-up: a new era for an old disease. Curr. Opin. Infect. Dis. 28, 53–60 (2015).

    CAS  PubMed  Google Scholar 

  38. Unemo, M. & Ison, C. in Laboratory Diagnosis of Sexually Transmitted Infections, Including Human Immunodeficiency Virus (eds Unemo, M. et al.) 21–53 (WHO, 2013).

    Google Scholar 

  39. Katz, A. R. et al. False-positive gonorrhea test results with a nucleic acid amplification test: the impact of low prevalence on positive predictive value. Clin. Infect. Dis. 38, 814–819 (2004).

    PubMed  Google Scholar 

  40. Palmer, H. M., Mallinson, H., Wood, R. L. & Herring, A. J. Evaluation of the specificities of five DNA amplification methods for the detection of Neisseria gonorrhoeae. J. Clin. Microbiol. 41, 835–837 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Tabrizi, S. N. et al. Evaluation of six commercial nucleic acid amplification tests for detection of Neisseria gonorrhoeae and other Neisseria species. J. Clin. Microbiol. 49, 3610–3615 (2011).

    PubMed  PubMed Central  Google Scholar 

  42. Whiley, D. M., Tapsall, J. W. & Sloots, T. P. Nucleic acid amplification testing for Neisseria gonorrhoeae: an ongoing challenge. J. Mol. Diagn. 8, 3–15 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Golparian, D., Boräng, S., Sundqvist, M. & Unemo, M. Evaluation of the new BD Max GC real-time PCR assay, analytically and clinically as a supplementary test for the BD ProbeTec GC Qx Amplified DNA Assay, for molecular detection of Neisseria gonorrhoeae. J. Clin. Microbiol. 53, 3935–3937 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Smith, D. W., Tapsall, J. W. & Lum, G. Guidelines for the use and interpretation of nucleic acid detection tests for Neisseria gonorrhoeae in Australia: a position paper on behalf of the Public Health Laboratory Network. Commun. Dis. Intell. Q. Rep. 29, 358–365 (2005).

    PubMed  Google Scholar 

  45. Enriquez, R. P., Goire, N., Kundu, R., Gatus, B. J. & Lahra, M. M. A comparison of agar dilution with the Calibrated Dichotomous Sensitivity (CDS) and Etest methods for determining the minimum inhibitory concentration of ceftriaxone against Neisseria gonorrhoeae. Diagn. Microbiol. Infect. Dis. 86, 40–43 (2016).

    CAS  PubMed  Google Scholar 

  46. Low, N. & Unemo, M. Molecular tests for the detection of antimicrobial resistant Neisseria gonorrhoeae: when, where, and how to use? Curr. Opin. Infect. Dis. 29, 45–51 (2016).

    CAS  PubMed  Google Scholar 

  47. Low, N., Unemo, M., Jensen, J. S., Breuer, J. & Stephenson, J. M. Molecular diagnostics for gonorrhoea: implications for antimicrobial resistance and the threat of untreatable gonorrhoea. PLoS Med. 11, e1001598 (2014).

    PubMed  PubMed Central  Google Scholar 

  48. Goire, N. et al. Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance. Nat. Rev. Microbiol. 12, 223–229 (2014).

    CAS  PubMed  Google Scholar 

  49. Tapsall, J. W., Ndowa, F., Lewis, D. A. & Unemo, M. Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae. Expert Rev. Anti. Infect. Ther. 7, 821–834 (2009).

    PubMed  Google Scholar 

  50. Unemo, M., Golparian, D., Syversen, G., Vestrheim, D. F. & Moi, H. Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhoea treatment, Norway, 2010. Euro Surveill. 15, 19721 (2010).

    PubMed  Google Scholar 

  51. Ison, C. A., Hussey, J., Sankar, K. N., Evans, J. & Alexander, S. Gonorrhoea treatment failures to cefixime and azithromycin in England. Euro Surveill. 16, 19833 (2011).

    PubMed  Google Scholar 

  52. Unemo, M., Golparian, D., Stary, A. & Eigentler, A. First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhoea treatment failure in Austria, 2011. Euro Surveill. 16, 19998 (2011).

    PubMed  Google Scholar 

  53. Unemo, M. et al. 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, 1273–1280 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Allen, V. G. et al. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA 309, 163–170 (2013).

    CAS  PubMed  Google Scholar 

  55. Singh, A. E. et al. Gonorrhea treatment failures with oral and injectable expanded spectrum cephalosporin monotherapy versus dual therapy at 4 Canadian sexually transmitted infection clinics, 2010–2013. Sex. Transm. Dis. 42, 331–336 (2015).

    CAS  PubMed  Google Scholar 

  56. Lewis, D. A. et al. Phenotypic and genetic characterization of the first two cases of extended-spectrum cephalosporin resistant Neisseria gonorrhoeae infection in South Africa and association with cefixime treatment failure. J. Antimicrob. Chemother. 68, 1267–1270 (2013).

    CAS  PubMed  Google Scholar 

  57. Ohnishi, M. 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. 55, 3538–3545 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Tapsall, J. et al. Two cases of failed ceftriaxone treatment in pharyngeal gonorrhoea verified by molecular microbiological methods. J. Med. Microbiol. 58, 683–687 (2009).

    CAS  PubMed  Google Scholar 

  59. Chen, Y. M. et al. Failure of ceftriaxone 500 mg to eradicate pharyngeal gonorrhoea, Australia. J. Antimicrob. Chemother. 68, 1445–1447 (2013).

    CAS  Google Scholar 

  60. Read, P. J., Limnios, E. A., McNulty, A., Whiley, D. & Lahra, L. M. One confirmed and one suspected case of pharyngeal gonorrhoea treatment failure following 500 mg ceftriaxone in Sydney, Australia. Sex. Health 10, 460–462 (2013).

    PubMed  Google Scholar 

  61. Unemo, M., Golparian, D. & Hestner, A. Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010. Euro Surveill. 16, 1–3 (2011).

    Google Scholar 

  62. Golparian, D. et al. Four treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or cefotaxime (500 mg), Sweden, 2013 and 2014. Euro Surveill. 19, 20862 (2014).

    PubMed  Google Scholar 

  63. Unemo, M., Golparian, D., Potocˇnik, M. & Jeverica, S. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. Euro Surveill. 17, 1–4 (2012).

    Google Scholar 

  64. Cámara, J. et al. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J. Antimicrob. Chemother. 67, 1858–1860 (2012).

    PubMed  Google Scholar 

  65. Unemo, M., Shipitsyna, E. & Domeika, M. Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 East European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial. Sex. Transm. Infect. 86, 442–444 (2010).

    CAS  PubMed  Google Scholar 

  66. Tapsall, J. W. Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci. Sex. Transm. Infect. 85, 256–258 (2009).

    CAS  PubMed  Google Scholar 

  67. Japanese Society of Sexually Transmitted Infection. Gonococcal infection. Sexually transmitted infections, diagnosis and treatment guidelines 2011. Jpn J. Sex. Transm. Dis. 22 (Suppl. 1), 52–59 (2011).

  68. Ito, S. et al. Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis. J. Antimicrob. Chemother. 71, 2559–2562 (2016).

    CAS  PubMed  Google Scholar 

  69. Lewis, D. A. The gonococcus fights back: is this time a knock out? Sex. Transm. Infect. 86, 415–421 (2010).

    PubMed  Google Scholar 

  70. Unemo, M. et al. in Pathogenic Neisseria: Genomics, Molecular Biology and Disease Intervention Ch. 9 (eds Davies, J. K. & Kahler, C. M.) (Caister Academic Press, 2014).

    Google Scholar 

  71. Ito, M. et al. Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in Central Japan. Antimicrob. Agents Chemother. 49, 137–143 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Cole, M. J. et al. Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from the 2013 European surveillance. BMC Infect. Dis. 15, 321 (2015).

    PubMed  PubMed Central  Google Scholar 

  73. Kirkcaldy, R. D. et al. Neisseria gonorrhoeae antimicrobial susceptibility surveillance — the Gonococcal Isolate Surveillance Project, 27 sites, United States, 2014. MMWR Surveill. Summ. 65, 1–19 (2016).

    PubMed  Google Scholar 

  74. Chisholm, S. A. et al. An outbreak of high-level azithromycin resistant Neisseria gonorrhoeae in England. Sex. Transm. Infect. 92, 365–367 (2016).

    PubMed  Google Scholar 

  75. Demczuk, W. et al. Genomic epidemiology and molecular resistance mechanisms of azithromycin resistant Neisseria gonorrhoeae in Canada from 1997 to 2014. J. Clin. Microbiol. 54, 1304–1313 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Fifer, H. et al. Failure of dual antimicrobial therapy in treatment of gonorrhea. N. Engl. J. Med. 374, 2504–2506 (2016).

    PubMed  Google Scholar 

  77. Kirkcaldy, R. D. et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin. Infect. Dis. 59, 1083–1091 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Unemo, M. et al. In vitro activity of ertapenem versus ceftriaxone against Neisseria gonorrhoeae isolates with highly diverse ceftriaxone MIC values and effects of ceftriaxone resistance determinants — ertapenem for treatment of gonorrhea? Antimicrob. Agents Chemother. 56, 3603–3609 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Quaye, N., Cole, M. J. & Ison, C. A. Evaluation of the activity of ertapenem against gonococcal isolates exhibiting a range of susceptibilities to cefixime. J. Antimicrob. Chemother. 69, 1568–1571 (2014).

    CAS  PubMed  Google Scholar 

  80. Hauser, C., Hirzberger, L., Unemo, M., Furrer, H. & Endimiani, A. In vitro activity of fosfomycin alone and in combination with ceftriaxone or azithromycin against clinical Neisseria gonorrhoeae isolates. Antimicrob. Agents Chemother. 59, 1605–1611 (2015).

    PubMed  PubMed Central  Google Scholar 

  81. Brown, L. B. et al. Neisseria gonorrhoeae antimicrobial susceptibility in Lilongwe, Malawi, 2007. Sex. Transm. Dis. 37, 169–172 (2010).

    PubMed  Google Scholar 

  82. Chisholm, S. A. et al. An evaluation of gentamicin susceptibility of Neisseria gonorrhoeae isolates in Europe. J. Antimicrob. Chemother. 66, 592–595 (2011).

    CAS  PubMed  Google Scholar 

  83. Dowell, D. & Kirkcaldy, R. D. Effectiveness of gentamicin for gonorrhoea treatment: systematic review and meta-analysis. Sex. Transm. Infect. 89, 142–147 (2013).

    CAS  Google Scholar 

  84. Hathorn, E., Dhasmana, D., Duley, L. & Ross, J. D. The effectiveness of gentamicin in the treatment of Neisseria gonorrhoeae: a systematic review. Syst. Rev. 3, 104 (2014).

    PubMed  PubMed Central  Google Scholar 

  85. Lee, H., Lee, K. & Chong, Y. New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae. Expert Rev. Anti. Infect. Ther. 14, 243–256 (2016).

    CAS  PubMed  Google Scholar 

  86. Golparian, D., Fernandes, P., Ohnishi, M., Jensen, J. S. & Unemo, M. 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-potential treatment option for gonorrhea? Antimicrob. Agents Chemother. 56, 2739–2742 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Llano-Sotelo, B. et al. Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis. Antimicrob. Agents Chemother. 54, 4961–4970 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Still, J. G. et al. Pharmacokinetics of solithromycin (CEM-101) after single or multiple oral doses and effects of food on single-dose bioavailability in healthy adult subjects. Antimicrob. Agents Chemother. 55, 1997–2003 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Hook, E. W. III et al. A Phase 2 trial of oral solithromycin 1200 mg or 1000 mg as single-dose oral therapy for uncomplicated gonorrhea. Clin. Infect. Dis. 61, 1043–1048 (2015).

    PubMed  Google Scholar 

  90. Jacobsson, S. et al. 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, 5585–5588 (2014).

    PubMed  PubMed Central  Google Scholar 

  91. Huband, M. D. et al. 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, 467–474 (2015).

    PubMed  Google Scholar 

  92. Unemo, M. et al. High in vitro susceptibility to the novel spiropyrimidinetrione ETX0914 (also known as AZD0914) among 873 contemporary clinical Neisseria gonorrhoeae isolates in 21 European countries during 2012–2014. Antimicrob. Agents Chemother. 59, 5220–5225 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Foerster, S. et al. Genetic resistance determinants, in vitro time-kill curve analysis and pharmacodynamic functions for the novel topoisomerase II inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae. Front. Microbiol. 6, 1377 (2015).

    PubMed  PubMed Central  Google Scholar 

  94. Basarab, G. S. et al. Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial type II topoisomerases. Sci. Rep. 5, 11827 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Alm, R. A. et al. Characterization of the novel DNA gyrase inhibitor AZD0914: low resistance potential and lack of cross-resistance in Neisseria gonorrhoeae. Antimicrob. Agents Chemother. 59, 1478–1486 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Basarab, G. S. et al. Non-clinical safety profile of a novel gyrase inhibitor for treatment of Neisseria gonorrhoeae infections, poster F-268 [abstract]. 54th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, District of Columbia, USA (2014).

  97. Lawrence, K. O'Connor, K., Atuah, K., Matthews, D. & Gardner, H. Safety & pharmacokinetics of single escalating oral doses of A.Z.D.0914: a novel spiropyrimidinetrione antibacterial agent, poster F.-267 [abstract]. 54th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, District of Columbia, USA (2014).

  98. Su, X. H. et al. Multidrug-resistant Neisseria gonorrhoeae isolates from Nanjing, China, are sensitive to killing by a novel DNA Gyrase inhibitor, ETX0914 (AZD0914). Antimicrob. Agents Chemother. 60, 621–623 (2015).

    PubMed  PubMed Central  Google Scholar 

  99. US National Library of Medicine. ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT02210325 (2016).

  100. Taylor, S. N. et al. A phase II trial of single-dose oral ETX0914 (AZD0914) for treatment of uncomplicated urogenital gonorrhea [abstract 5B5]. 2016 STD Prevention Conference https://cdc.confex.com/cdc/std2016/webprogram/Paper37739.html (2016).

  101. Tully, J. G., Taylor-Robinson, D., Cole, R. M. & Rose, D. L. A newly discovered mycoplasma in the human urogenital tract. Lancet 1, 1288–1291 (1981).

    CAS  PubMed  Google Scholar 

  102. Samra, Z., Borin, M., Bukowsky, Y., Lipshitz, Y. & Sompolinsky, D. Non-occurrence of Mycoplasma genitalium in clinical specimens. Eur. J. Clin. Microbiol. Infect. Dis. 7, 49–51 (1988).

    CAS  PubMed  Google Scholar 

  103. Jensen, J. S., Hansen, H. T. & Lind, K. Isolation of Mycoplasma genitalium strains from the male urethra. J. Clin. Microbiol. 34, 286–291 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Hamasuna, R., Osada, Y. & Jensen, J. S. Antibiotic susceptibility testing of Mycoplasma genitalium by TaqMan 5′ nuclease real-time PCR. Antimicrob. Agents Chemother. 49, 4993–4998 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Jensen, J. S., Bradshaw, C. S., Tabrizi, S. N., Fairley, C. K. & Hamasuna, R. Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with induced macrolide resistance. Clin. Infect. Dis. 47, 1546–1553 (2008).

    CAS  PubMed  Google Scholar 

  106. Jensen, J. S., Uldum, S. A., Søndergård-Andersen, J., Vuust, J. & Lind, K. Polymerase chain reaction for detection of Mycoplasma genitalium in clinical samples. J. Clin. Microbiol. 29, 46–50 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Palmer, H. M., Gilroy, C. B., Furr, P. M. & Taylor-Robinson, D. Development and evaluation of the polymerase chain reaction to detect Mycoplasma genitalium. FEMS Microbiol. Lett. 61, 199–203 (1991).

    CAS  PubMed  Google Scholar 

  108. Daley, G., Russell, D., Tabrizi, S. & McBride, J. Mycoplasma genitalium: a review. Int. J. STD AIDS 25, 475–487 (2014).

    CAS  PubMed  Google Scholar 

  109. Lis, R., Rowhani-Rahbar, A. & Manhart, L. E. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin. Infect. Dis. 61, 418–426 (2015).

    PubMed  Google Scholar 

  110. Jensen, J. S. et al. Mycoplasma genitalium: a cause of male urethritis? Genitourin. Med. 69, 265–269 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Horner, P. J., Gilroy, C. B., Thomas, B. J., Naidoo, R. O. & Taylor-Robinson, D. Association of Mycoplasma genitalium with acute non-gonococcal urethritis. Lancet 342, 582–585 (1993).

    CAS  PubMed  Google Scholar 

  112. Falk, L., Fredlund, H. & Jensen, J. S. Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis. Sex. Transm. Infect. 80, 289–293 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Björnelius, E., Lidbrink, P. & Jensen, J. S. Mycoplasma genitalium in non-gonococcal urethritis — a study in Swedish male STD patients. Int. J. STD AIDS 11, 292–296 (2000).

    PubMed  Google Scholar 

  114. Horner, P. J. & Taylor-Robinson, D. Mycoplasma genitalium and non-gonococcal urethritis. Lancet 343, 790–791 (1994).

    CAS  PubMed  Google Scholar 

  115. Bradshaw, C. S. et al. Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure. J. Infect. Dis. 193, 336–345 (2006).

    PubMed  Google Scholar 

  116. Wikström, A. & Jensen, J. S. Mycoplasma genitalium: a common cause of persistent urethritis among men treated with doxycycline. Sex. Transm. Infect. 82, 276–279 (2006).

    PubMed  PubMed Central  Google Scholar 

  117. Frølund, M., Björnelius, E., Lidbrink, P., Ahrens, P. & Jensen, J. S. Urethritis-associated pathogens in urine from men with non-gonococcal urethritis: a case-control study. Acta Derm. Venereol. 96, 689–694 (2016).

    PubMed  Google Scholar 

  118. Jensen, J. S. & Bradshaw, C. Management of Mycoplasma genitalium infections — can we hit a moving target? BMC Infect. Dis. 15, 343 (2015).

    PubMed  PubMed Central  Google Scholar 

  119. Cohen, C. R. et al. Association between Mycoplasma genitalium and acute endometritis. Lancet 359, 765–766 (2002).

    PubMed  Google Scholar 

  120. Manhart, L. E. et al. Mucopurulent cervicitis and Mycoplasma genitalium. J. Infect. Dis. 187, 650–657 (2003).

    PubMed  Google Scholar 

  121. Anagrius, C., Loré, B. & Jensen, J. S. Mycoplasma genitalium: prevalence, clinical significance, and transmission. Sex. Transm. Infect. 81, 458–462 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Falk, L., Fredlund, H. & Jensen, J. S. Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection. Sex. Transm. Infect. 81, 73–78 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Oakeshott, P. et al. Prevalence of Mycoplasma genitalium in early pregnancy and relationship between its presence and pregnancy outcome. BJOG 111, 1464–1467 (2004).

    PubMed  Google Scholar 

  124. Edlund, M., Blaxhult, A. & Bratt, G. The spread of Mycoplasma genitalium among men who have sex with men. Int. J. STD AIDS 23, 455–456 (2012).

    CAS  PubMed  Google Scholar 

  125. Soni, S. et al. The prevalence of urethral and rectal Mycoplasma genitalium and its associations in men who have sex with men attending a genitourinary medicine clinic. Sex. Transm. Infect. 86, 21–24 (2010).

    CAS  PubMed  Google Scholar 

  126. Lillis, R. A., Nsuami, M. J., Myers, L. & Martin, D. H. Utility of urine, vaginal, cervical, and rectal specimens for detection of Mycoplasma genitalium in women. J. Clin. Microbiol. 49, 1990–1992 (2011).

    PubMed  PubMed Central  Google Scholar 

  127. Jensen, J. S., Björnelius, E., Dohn, B. & Lidbrink, P. Comparison of first void urine and urogenital swab specimens for detection of Mycoplasma genitalium and Chlamydia trachomatis by polymerase chain reaction in patients attending a sexually transmitted disease clinic. Sex. Transm. Dis. 31, 499–507 (2004).

    CAS  PubMed  Google Scholar 

  128. Sonnenberg, P. et al. Epidemiology of Mycoplasma genitalium in British men and women aged 16–44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Int. J. Epidemiol. 44, 1982–1994 (2015).

    PubMed  PubMed Central  Google Scholar 

  129. Hamasuna, R., Osada, Y. & Jensen, J. S. Isolation of Mycoplasma genitalium from first-void urine specimens by coculture with Vero cells. J. Clin. Microbiol. 45, 847–850 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Tabrizi, S. N. et al. Evaluation of the Hologic Panther transcription mediated amplification assay for detection of Mycoplasma genitalium. J. Clin. Microbiol. 54, 2201–2203 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Taylor-Robinson, D., Gilroy, C. B. & Jensen, J. S. The biology of Mycoplasma genitalium. Venereology 13, 119–127 (2000).

    Google Scholar 

  132. Hamasuna, R., Jensen, J. S. & Osada, Y. Antimicrobial susceptibilities of Mycoplasma genitalium by broth dilution and quantitative PCR. Antimicrob. Agents Chemother. 53, 4938–4939 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Jensen, J. S., Fernandes, P. & Unemo, M. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against macrolide-resistant and -susceptible Mycoplasma genitalium strains. Antimicrob. Agents Chemother. 58, 3151–3156 (2014).

    PubMed  PubMed Central  Google Scholar 

  134. Waites, K. B. et al. Standardized methods and quality control limits for agar and broth microdilution susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum. J. Clin. Microbiol. 50, 3542–3547 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Bradshaw, C. S. et al. Azithromycin failure in Mycoplasma genitalium urethritis. Emerg. Infect. Dis. 12, 1149–1152 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Renaudin, H., Tully, J. G. & Bebear, C. In-vitro susceptibilities of Mycoplasma genitalium to antibiotics. Antimicrob. Agents Chemother. 36, 870–872 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Hannan, P. C. Comparative susceptibilities of various AIDS-associated and human urogenital tract mycoplasmas and strains of Mycoplasma pneumoniae to 10 classes of antimicrobial agent in vitro. J. Med. Microbiol. 47, 1115–1122 (1998).

    CAS  PubMed  Google Scholar 

  138. Twin, J. et al. Transmission and selection of macrolide resistant Mycoplasma genitalium infections detected by rapid high resolution melt analysis. PLoS ONE 7, e35593 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Jensen, J. S. in Diagnosis of Sexually Transmitted Diseases: Methods and Protocols (eds MacKenzie, C. R. & Henrich, B.) 129–139 (Humana Press, 2012).

    Google Scholar 

  140. Touati, A., Peuchant, O., Jensen, J. S., Bebear, C. & Pereyre, S. Direct detection of macrolide resistance in Mycoplasma genitalium isolates from clinical specimens from France by use of real-time PCR and melting curve analysis. J. Clin. Microbiol. 52, 1549–1555 (2014).

    PubMed  PubMed Central  Google Scholar 

  141. Wold, C. et al. Identification of macrolide-resistant Mycoplasma genitalium using real-time PCR. J. Eur. Acad. Dermatol. Venereol. 29, 1616–1620 (2015).

    CAS  PubMed  Google Scholar 

  142. Tabrizi, S. N. et al. Multiplex assay for simultaneous detection of Mycoplasma genitalium and macrolide resistance using PlexZyme and PlexPrime technology. PLoS ONE 11, e0156740 (2016).

    PubMed  PubMed Central  Google Scholar 

  143. Thellin, O. et al. Multiplex real-time PCR assay targeting macrolide resistance mutations in Mycoplasma genitalium [abstract P0926]. 26th European Congress of Clinical Microbiology and Infectious Diseases https://www.escmid.org/escmid_publications/escmid_elibrary/?q=thellin&id=2173&L=0&x=0&y=0 (2016).

  144. Deguchi, T. et al. Analysis of the gyrA and parC genes of Mycoplasma genitalium detected in first-pass urine of men with non-gonococcal urethritis before and after fluoroquinolone treatment. J. Antimicrob. Chemother. 48, 742–744 (2001).

    CAS  PubMed  Google Scholar 

  145. Walker, S. et al. Simultaneous detection of Mycoplasma genitalium and key mutations conferring resistance to fluoroquinolone antibiotics using a novel real-time QPCR technology [abstract S5]. 21st Congress of the International Organization for Mycoplasmology (2016).

  146. Pond, M. J. et al. High prevalence of antibiotic-resistant Mycoplasma genitalium in nongonococcal urethritis: the need for routine testing and the inadequacy of current treatment options. Clin. Infect. Dis. 58, 631–637 (2014).

    CAS  PubMed  Google Scholar 

  147. Kikuchi, M. et al. Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan. J. Antimicrob. Chemother. 69, 2376–2382 (2014).

    CAS  PubMed  Google Scholar 

  148. Shimada, Y. et al. Emergence of clinical strains of Mycoplasma genitalium harbouring alterations in ParC associated with fluoroquinolone resistance. Int. J. Antimicrob. Agents 36, 255–258 (2010).

    PubMed  Google Scholar 

  149. Martin, D. H. et al. A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. N. Engl. J. Med. 327, 921–925 (1992).

    CAS  PubMed  Google Scholar 

  150. Horner, P., Blee, K. & Adams, E. Time to manage Mycoplasma genitalium as an STI: but not with azithromycin 1 g! Curr. Opin. Infect. Dis. 27, 68–74 (2014).

    CAS  PubMed  Google Scholar 

  151. Björnelius, E. et al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial. Sex. Transm. Infect. 84, 72–76 (2008).

    PubMed  Google Scholar 

  152. Manhart, L. E., Jensen, J. S., Bradshaw, C. S., Golden, M. R. & Martin, D. H. Efficacy of antimicrobial therapy for Mycoplasma genitalium infections. Clin. Infect. Dis. 61 (Suppl. 8), S802–S817 (2015).

    CAS  PubMed  Google Scholar 

  153. Gesink, D. C. et al. Mycoplasma genitalium presence, resistance and epidemiology in Greenland. Int. J. Circumpolar Health 71, 1–8 (2012).

    PubMed  Google Scholar 

  154. Guschin, A., Ryzhikh, P., Rumyantseva, T., Gomberg, M. & Unemo, M. Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin. BMC Infect. Dis. 15, 40 (2015).

    PubMed  PubMed Central  Google Scholar 

  155. Pereyre, S. et al. In vitro selection and characterization of resistance to macrolides and related antibiotics in Mycoplasma pneumoniae. Antimicrob. Agents Chemother. 48, 460–465 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Johannisson, G. et al. Occurrence and treatment of Mycoplasma genitalium in patients visiting STD clinics in Sweden. Int. J. STD AIDS 11, 324–326 (2000).

    CAS  PubMed  Google Scholar 

  157. Maeda, S. I. et al. Association of Mycoplasma genitalium persistence in the urethra with recurrence of nongonococcal urethritis. Sex. Transm. Dis. 28, 472–476 (2001).

    CAS  PubMed  Google Scholar 

  158. Yasuda, M., Maeda, S. & Deguchi, T. In vitro activity of fluoroquinolones against Mycoplasma genitalium and their bacteriological efficacy for treatment of M. genitalium-positive nongonococcal urethritis in men. Clin. Infect. Dis. 41, 1357–1359 (2005).

    CAS  PubMed  Google Scholar 

  159. Takahashi, S. et al. Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis. J. Infect. Chemother. 17, 392–396 (2011).

    CAS  PubMed  Google Scholar 

  160. Terada, M., Izumi, K., Ohki, E., Yamagishi, Y. & Mikamo, H. Antimicrobial efficacies of several antibiotics against uterine cervicitis caused by Mycoplasma genitalium. J. Infect. Chemother. 18, 313–317 (2012).

    CAS  PubMed  Google Scholar 

  161. Bradshaw, C. S., Chen, M. Y. & Fairley, C. K. Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS ONE 3, e3618 (2008).

    PubMed  PubMed Central  Google Scholar 

  162. Gundevia, Z., Foster, R., Jamil, M. S. & McNulty, A. Positivity at test of cure following first-line treatment for genital Mycoplasma genitalium: follow-up of a clinical cohort. Sex. Transm. Infect. 91, 11–13 (2015).

    PubMed  Google Scholar 

  163. Bissessor, M. et al. Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens. Clin. Infect. Dis. 60, 1228–1236 (2015).

    CAS  PubMed  Google Scholar 

  164. Tagg, K. A., Jeoffreys, N. J., Couldwell, D. L., Donald, J. A. & Gilbert, G. L. Fluoroquinolone and macrolide resistance-associated mutations in Mycoplasma genitalium. J. Clin. Microbiol. 51, 2245–2249 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Falk, L., Fredlund, H. & Jensen, J. S. Tetracycline treatment does not eradicate Mycoplasma genitalium. Sex. Transm. Infect. 79, 318–319 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Dallas, S. D. et al. Development of doxycycline MIC and disk diffusion interpretive breakpoints and revision of tetracycline breakpoints for Streptococcus pneumoniae. J. Clin. Microbiol. 51, 1798–1802 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Ito, S. et al. Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100- mg twice-daily dose regimen of sitafloxacin. J. Infect. Chemother. 18, 414–418 (2012).

    CAS  PubMed  Google Scholar 

  168. Takahashi, S. et al. Clinical efficacy of sitafloxacin 100 mg twice daily for 7 days for patients with non-gonococcal urethritis. J. Infect. Chemother. 19, 941–945 (2013).

    CAS  PubMed  Google Scholar 

  169. Ito, S. et al. Prediction of the persistence of Mycoplasma genitalium after antimicrobial chemotherapy by quantification of leukocytes in first-void urine from patients with non-gonococcal urethritis. J. Infect. Chemother. 20, 298–302 (2014).

    CAS  PubMed  Google Scholar 

  170. Paukner, S., Sader, H. S., Ivezic-Schoenfeld, Z. & Jones, R. N. Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 2010. Antimicrob. Agents Chemother. 57, 4489–4495 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Paukner, S., Gruss, A., Fritsche, T. R., Ivezic-Schoenfeld, Z. & Jones, R. N. In vitro activity of the novel pleuromutilin BC-3781 tested against bacterial pathogens causing sexually transmitted diseases (STD). Interscience Conference of Antimicrobial Agents and Chemotherapy E-1183 (2014).

  172. Prince, W. T. et al. Phase II clinical study of BC-3781, a pleuromutilin antibiotic, in treatment of patients with acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother. 57, 2087–2094 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Waites, K. B., Crabb, D. M., Duffy, L. B. & Huband, M. D. In vitro antibacterial activity of AZD0914 against human mycoplasmas and ureaplasmas. Antimicrob. Agents Chemother. 59, 3627–3629 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Geisler, W. M. et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N. Engl. J. Med. 373, 2512–2521 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Falk, L., Enger, M. & Jensen, J. S. Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women. J. Antimicrob. Chemother. 70, 3134–3140 (2015).

    CAS  PubMed  Google Scholar 

  176. Ndowa, F., Lusti-Narasimhan, M. & Unemo, M. 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, 317–318 (2012).

    PubMed  Google Scholar 

  177. Lewis, D. A. Will targeting oropharyngeal gonorrhoea delay the further emergence of drug-resistant Neisseria gonorrhoeae strains? Sex. Transm. Infect. 91, 234–237 (2015).

    CAS  PubMed  Google Scholar 

  178. Donà, V. et al. Multiplex real-time PCR with high-resolution melting analysis for the characterization of antimicrobial resistance in Neisseria gonorrhoeae. J. Clin. Microbiol. 54, 2074–2081 (2016).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Work at the WHO Collaborating Centre for Gonorrhoea and other STIs is supported by Örebro University Hospital, Department of Laboratory Medicine, the Research Committee of Örebro County and the Örebro University Hospital Foundation, Örebro, Sweden.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, SE-701 85, Sweden

    Magnus Unemo

  2. Department of Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Artillerivej 5, Copenhagen S, DK-2300, Denmark

    Jorgen S. Jensen

Authors
  1. Magnus Unemo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jorgen S. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors researched data for the article, made substantial contribution to discussion of its content, wrote and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Magnus Unemo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

FURTHER INFORMATION

GTOG trail website

PowerPoint slides

Glossary

Homotypic resistance

The whole population of a bacterial strain is genetically or phenotypically resistant to an antimicrobial if all cells contain one or several resistance mutations or according to the measured MIC of the antimicrobial, respectively.

Test-of-cure

(TOC). Test performed at a follow-up visit of patients after treatment to ensure that the infection is eradicated and the patient cured.

Escherichia coli numbering

Number of the nucleotide or amino acid position in the genome of E. coli.

Nucleic acid amplification tests

(NAATs). Molecular diagnostic tests that amplify and subsequently detect nucleic acid (DNA/RNA) specific for the pathogen.

Point-of-care NAATs

Molecular diagnostic tests that amplify and subsequently detect nucleic acid (DNA or RNA) specific for the pathogen and that can be performed on site without laboratory facilities.

Agar dilution

Gold-standard method, using antimicrobial incorporated in the culture media, for determination of antimicrobial susceptibility in N. gonorrhoeae.

Etest

Frequently used method, utilizing antimicrobial gradient strips, for determination of antimicrobial susceptibility in N. gonorrhoeae.

Minimum inhibitory concentration

(MIC). Minimum concentration of an antimicrobial that completely inhibits the growth of bacteria.

Breakpoint

MIC value that distinguishes susceptible or resistant isolates.

M. genitalium numbering

Number of the nucleotide or amino acid position in the genome of M. genitalium.

Pharmacokinetic–pharmacodynamic calculations

Calculations or simulations of the pharmacokinetics (fate of the drug from uptake and metabolism to elimination when administered to humans) and/or pharmacodynamics (biochemical and physiological effects) of a drug.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Unemo, M., Jensen, J. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium. Nat Rev Urol 14, 139–152 (2017). https://doi.org/10.1038/nrurol.2016.268

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2016.268

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing